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Bartlett, John Alexander

Overview:

My clinical investigation is focused on the pathogenesis and treatment of HIV infection and its complicastions, especially in resource-limited settings.

Key Words: HIV infection, AIDS, treatment strategies, treatment failure, co-infections, resource-limited settings

Positions:

Professor of Medicine

Medicine, Infectious Diseases
School of Medicine

Research Professor of Global Health

Duke Global Health Institute
Institutes and Provost's Academic Units

Professor in the School of Nursing

School of Nursing
School of Nursing

Affiliate of the Duke Initiative for Science & Society

Duke Science & Society
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Director of the AIDS Research and Treatment Center

Medicine
School of Medicine

Education:

M.D. 1981

M.D. — University of Virginia

Medical Resident, Medicine

Duke University

Fellow In Infectious Diseases, Medicine

Duke University

News:

Grants:

Viral Zoonoses and Severe Febrile Illness in Northern Tanzania

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
July 06, 2016
End Date
June 30, 2021

Interdisciplinary Research Training Program in AIDS

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2010
End Date
August 31, 2020

Integrating Mental Health into HIV Clinic to Improve Outcomes in Tanzanian Youth

Administered By
Pediatrics, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
July 01, 2015
End Date
June 30, 2020

Mid Southern Primary Care Networks Node

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
September 01, 2015
End Date
May 31, 2020

Addressing High Risk Alcohol Use Amongst Injury Patients in an Emergency Department in Tanzania

Administered By
Duke Global Health Institute
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 23, 2015
End Date
August 31, 2019

Sociobehavioral Sciences Research to Improve Care for HIV Infection in Tanzania

Administered By
Duke Global Health Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2013
End Date
January 31, 2018

MEPI 2 Tanzania

Administered By
Duke Global Health Institute
AwardedBy
Kilimanjaro Christian Medical Centre
Role
Principal Investigator
Start Date
August 28, 2015
End Date
July 31, 2017

HIV and Asthma in the Post- ART Era

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 13, 2014
End Date
August 31, 2016

KCM College-Duke Medical Educational Partnership (DUKE)

Administered By
Duke Global Health Institute
AwardedBy
Kilimanjaro Christian Medical Centre
Role
Principal Investigator
Start Date
September 01, 2010
End Date
August 31, 2016

Ryan White HIV Adult ID Services, Year 7

Administered By
Medicine, Infectious Diseases
AwardedBy
Wake County Human Services
Role
Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2016

Risk Factors for Atherosclerosis among Patients with Heart Failure in Kenya

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 16, 2011
End Date
July 31, 2015

Developing Research Capacity on HIV-Associated Malignancies (D43)

Administered By
Duke Global Health Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 27, 2010
End Date
July 31, 2015

5UM1-AI069484-07 Supplement

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 01, 2007
End Date
December 31, 2014

HIV/AIDS Clinical Trials Unit and Research Sites

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 01, 2007
End Date
December 31, 2014

AIDS International Training and Research Program

Administered By
Duke Global Health Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 01, 2003
End Date
May 31, 2014

Pregnancy and Response to Antiretroviral Therapy in South Africa

Administered By
Duke Global Health Institute
AwardedBy
National Institutes of Health
Role
Advisor
Start Date
September 27, 2010
End Date
August 31, 2013

Fatigue in HIV Positive People

Administered By
School of Nursing
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2004
End Date
August 31, 2010

International Clinical Trials Unit

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 2004
End Date
August 31, 2009

Role of Virus Recombination in Multiple Drug Resistance

Administered By
Medicine, Duke Human Vaccine Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
January 01, 2003
End Date
December 31, 2008

HIV/AIDS Clinical Trials Unit (IMPAACT CTU)

Administered By
Pediatrics, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 2007
End Date
November 30, 2008

IMPAACT CTU

Administered By
Pediatrics, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 01, 2007
End Date
November 30, 2008

K24 Mid-career Clinical Investigator Award

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2000
End Date
May 31, 2007

Early Intervention Services with Respect to HIV Disease in the Northern Outreach Clinic

Administered By
Medicine, Infectious Diseases
AwardedBy
Health Resources and Service Administration (HRSA)
Role
Principal Investigator
Start Date
September 30, 2000
End Date
March 31, 2007

Adult AIDS Clinical Trials Unit

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1996
End Date
December 31, 2006

Adult AIDS Clinical Trials Unit (Administrative Supplement 2)

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1996
End Date
December 31, 2006

(PETS) Peer Training to Empower, Education and Advocate

Administered By
Medicine, Infectious Diseases
AwardedBy
Department of Health and Human Services
Role
Principal Investigator
Start Date
September 30, 2002
End Date
December 31, 2005

Positive Connections - A peer Prevention Program and RAP - Resist all pressure: A peer Intervention Program for At-risk

Administered By
Medicine, Infectious Diseases
AwardedBy
Department of Health and Human Services
Role
Principal Investigator
Start Date
September 30, 2002
End Date
September 29, 2005

Adult Aids Clinical Trials Unit

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1996
End Date
December 31, 2004

Adults AIDS Clinical Trial Unit

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1996
End Date
August 09, 2003

Aids Research

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1989
End Date
May 31, 2002

Medications Effect on Taste and Smell

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Administrative Assistant
Start Date
August 01, 1996
End Date
January 31, 2000

Adult Aids Clinical Trials Unit

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1996
End Date
December 31, 1999

Duke University Adult Aids Clinical Trails Unit

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1996
End Date
December 31, 1999

Viral Control And Immune Reconstitution In Hiv Infection

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1996
End Date
August 31, 1999

Viral Control & Immune Reconstitution In Hiv Infection

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1999

Effect Of Medications On Taste And Smell In Hiv

Administered By
Psychiatry & Behavioral Sciences, Medical Psychology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
August 01, 1996
End Date
July 31, 1999

Duke University Center For Aids Research

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
July 01, 1994
End Date
June 30, 1999

General Clinical Research Center (Cru)

Administered By
Medicine, Rheumatology and Immunology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
October 01, 1975
End Date
November 30, 1998

Adoptive Immunotherapy For Aids Lymphoma

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1993
End Date
August 31, 1996

Duke University Center For Aids Research

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
July 01, 1993
End Date
June 30, 1994

The Establishment Of An Aids Treatment Evaluation Unit

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1991
End Date
December 31, 1991
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Publications:

Antiretroviral treatment and time since HIV-1 diagnosis are associated with large artery stiffness in sub-Saharan African HIV-1 patients

Authors
Msoka, TF; Van Guilder, GP; Smulders, YM; van Furth, M; Bartlett, JA; van Agtmael, MA
MLA Citation
Msoka, TF, Van Guilder, GP, Smulders, YM, van Furth, M, Bartlett, JA, and van Agtmael, MA. "Antiretroviral treatment and time since HIV-1 diagnosis are associated with large artery stiffness in sub-Saharan African HIV-1 patients." Artery Research 16 (December 2016): 34-41.
Source
crossref
Published In
Artery Research
Volume
16
Publish Date
2016
Start Page
34
End Page
41
DOI
10.1016/j.artres.2016.09.002

Association of knowledge on ART line of treatment, scarcity of treatment options and adherence.

Adherence to Antiretroviral Therapy (ART) is critical piece in the management of HIV infected patients. Despite the benefits of ART, non-adherence to ART persists. This study explores association between patient's knowledge of the ART line of treatment, availability of future treatment options and adherence.A cross sectional survey of HIV infected adolescent and adults was conducted. Cumulative optimal and sub-optimal adherence was defined as percentage adherence of ≥ 95 % and < 95 %, respectively. Binomial regression models were used to assess the association of patient's knowledge of the ART line of treatment, availability of future treatment options and adherence.Of the 402 patients reviewed, 101 (25.1 %) patients knew their ART line of treatment and were aware that future treatment options are limited. Compared to those who were not aware of the ART line of treatment and/or scarcity of future treatment options, those who were aware were more likely to be adherent (adjusted prevalence ratio [APR], 1.1; 95 % CI, 1.0-1.3).The study reports knowledge of patient's ART line of treatment and future treatment options is important indicator of adherence to ART. Although majority of the patients did not have the knowledge, those who had the knowledge demonstrated to be more adherent. It is critical for the physicians/health care providers in these settings to clearly educate patients about ART line of treatment and limited availability of future treatment options as such information is likely to influence individual behavior and improve patient's adherence to ART.

Authors
Ramadhani, HO; Muiruri, C; Maro, VP; Omondi, M; Mushi, JB; Lirhunde, ES; Bartlett, JA
MLA Citation
Ramadhani, HO, Muiruri, C, Maro, VP, Omondi, M, Mushi, JB, Lirhunde, ES, and Bartlett, JA. "Association of knowledge on ART line of treatment, scarcity of treatment options and adherence." BMC health services research 16 (July 15, 2016): 265-.
PMID
27416836
Source
epmc
Published In
BMC Health Services Research
Volume
16
Publish Date
2016
Start Page
265
DOI
10.1186/s12913-016-1483-6

Enhancing future acceptance of rural placement in Tanzania through peripheral hospital rotations for medical students.

Mal-distribution of health care workers is a global health challenge that exacerbates health disparities, especially in resource-limited settings. Interventions to mitigate the problem have targeted qualified personnel with little focus on medical students. However, studies have demonstrated that rural rotations positively influence students to practice in rural settings upon graduation. To evaluate the influence of peripheral rotations in a resource-limited setting, the Kilimanjaro Christian Medical University College introduced a 12-week clerkship rotation in peripheral hospitals for third-year medical (MD3) students in 2012. We administered an end-of-rotation survey to assess student perceptions, and attitudes toward rural practice after graduation.Questionnaires were voluntarily and anonymously administered to MD3 students in April 2014. The questions assessed perceptions of the experience, and attitudes towards rural practice upon graduation. The perceptions were assessed using strength of consensus measures (sCns). The effect of the experience on likelihood for rural practice was assessed using Crude Odds Ratio (COR), and predictors using Adjusted Odds Ratio (AOR) with 95 % Confidence Intervals (CI) tested at a 5 % level of significance. Variation was assessed using Hosmer and Lemeshow test Chi-square.111 out of 148 MD3 students participated; 62 % were male; 62 % <25 years old; and 72 % matriculated directly from secondary school. Overall, 81 % of MD3 students were satisfied with rural rotations (sCns = 83 %). The likelihood of accepting rural practice deployment after graduation was predicted by satisfaction with the peripheral hospital rotation program (AOR, 4.32; 95 % CI, 1.44-12.96; p, 0.009) and being male (AOR, 2.73; 95 % CI, 1.09-6.84; p, 0.032). Students admitted in medical school after health-related practice trended toward a higher likelihood of accepting rural practice after graduation compared to those enrolled directly from secondary school, although the difference was not significant (AOR, 4.99; 95 % CI, 0.88-28.41; p, 0.070). The Hosmer and Lemeshow test p-value was 0.686, indicating a good fit of the model. No significant differences in satisfaction between these two groups were observed, and also no significant differences between students born in rural areas compared to those born in urban areas existed.Results indicate that satisfaction with rural rotations is associated with increased likelihood of rural practice after graduation. We conclude that opportunities may exist to reduce mal-distribution of healthcare workers through interventions that target medical students.

Authors
Kapanda, GE; Muiruri, C; Kulanga, AT; Tarimo, CN; Lisasi, E; Mimano, L; Mteta, K; Bartlett, JA
MLA Citation
Kapanda, GE, Muiruri, C, Kulanga, AT, Tarimo, CN, Lisasi, E, Mimano, L, Mteta, K, and Bartlett, JA. "Enhancing future acceptance of rural placement in Tanzania through peripheral hospital rotations for medical students." BMC medical education 16 (February 9, 2016): 51-.
PMID
26861915
Source
epmc
Published In
BMC Medical Education
Volume
16
Publish Date
2016
Start Page
51
DOI
10.1186/s12909-016-0582-8

The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania.

Background.  Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers' confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes. Methods.  A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happened at <3 and ≥3 months, respectively, after failure diagnosis was made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing OI. Results.  Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of OI (adjusted hazards ratio [AHR], 0.4; 95% CI, .2-.6). Compared with patients who received timely switch after failure diagnosis was made, those who delayed switching were more likely to develop OI (AHR, 2.2; 95% CI, 1.1-4.3). Conclusion.  Delayed switching to second-line ART after failure diagnosis may increase the risk of OI. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.

Authors
Ramadhani, HO; Bartlett, JA; Thielman, NM; Pence, BW; Kimani, SM; Maro, VP; Mwako, MS; Masaki, LJ; Mmbando, CE; Minja, MG; Lirhunde, ES; Miller, WC
MLA Citation
Ramadhani, HO, Bartlett, JA, Thielman, NM, Pence, BW, Kimani, SM, Maro, VP, Mwako, MS, Masaki, LJ, Mmbando, CE, Minja, MG, Lirhunde, ES, and Miller, WC. "The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania." Open forum infectious diseases 3.1 (January 29, 2016): ofw018-.
PMID
26949717
Source
epmc
Published In
Open Forum Infectious Diseases
Volume
3
Issue
1
Publish Date
2016
Start Page
ofw018
DOI
10.1093/ofid/ofw018

Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection

Authors
Derache, A; Wallis, CL; Vardhanabhuti, S; Bartlett, J; Kumarasamy, N; Katzenstein, D
MLA Citation
Derache, A, Wallis, CL, Vardhanabhuti, S, Bartlett, J, Kumarasamy, N, and Katzenstein, D. "Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection." Journal of Infectious Diseases 213.2 (January 15, 2016): 250-256.
Source
crossref
Published In
Journal of Infectious Diseases
Volume
213
Issue
2
Publish Date
2016
Start Page
250
End Page
256
DOI
10.1093/infdis/jiv383

Lopinavir/Ritonavir Monotherapy as Second-line Antiretroviral Treatment in Resource-Limited Settings: Week 104 Analysis of AIDS Clinical Trials Group (ACTG) A5230.

The AIDS Clinical Trials Group (ACTG) A5230 study evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure (VF) on first-line human immunodeficiency virus (HIV) regimens in Africa and Asia.Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000 copies/mL. All subjects received LPV/r 400/100 mg twice daily. VF was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models.One hundred twenty-three subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 of 123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39 of 41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400 copies/mL over 104 weeks on LPV/r monotherapy was 60% (95% CI, 50%-68%); 80%-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level <400 copies/mL at weeks 24, 48, and 104 revealed that 61%, 62%, and 65% were suppressed to <40 copies/mL, respectively.LPV/r monotherapy after first-line VF with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.NCT00357552.

Authors
Kumarasamy, N; Aga, E; Ribaudo, HJ; Wallis, CL; Katzenstein, DA; Stevens, WS; Norton, MR; Klingman, KL; Hosseinipour, MC; Crump, JA; Supparatpinyo, K; Badal-Faesen, S; Bartlett, JA
MLA Citation
Kumarasamy, N, Aga, E, Ribaudo, HJ, Wallis, CL, Katzenstein, DA, Stevens, WS, Norton, MR, Klingman, KL, Hosseinipour, MC, Crump, JA, Supparatpinyo, K, Badal-Faesen, S, and Bartlett, JA. "Lopinavir/Ritonavir Monotherapy as Second-line Antiretroviral Treatment in Resource-Limited Settings: Week 104 Analysis of AIDS Clinical Trials Group (ACTG) A5230." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 60.10 (May 2015): 1552-1558.
Website
http://hdl.handle.net/10161/13768
PMID
25694653
Source
epmc
Published In
Clinical Infectious Diseases
Volume
60
Issue
10
Publish Date
2015
Start Page
1552
End Page
1558
DOI
10.1093/cid/civ109

Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Authors
Rubach, MP; Maro, VP; Bartlett, JA; Crump, JA
MLA Citation
Rubach, MP, Maro, VP, Bartlett, JA, and Crump, JA. "Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy." The American journal of tropical medicine and hygiene 92.2 (February 2015): 454-462.
Website
http://hdl.handle.net/10161/13771
PMID
25385866
Source
epmc
Published In
American Journal of Tropical Medicine and Hygiene
Volume
92
Issue
2
Publish Date
2015
Start Page
454
End Page
462
DOI
10.4269/ajtmh.14-0496

Initiation of antiretroviral therapy in HIV-infected adults with skin complaints in northern Tanzania.

Abnormal skin findings are identified in over 90% of human immunodeficiency virus (HIV)-infected persons globally. A prospective cohort study of HIV-infected patients with skin complaints commencing antiretroviral therapy (ART) in northern Tanzania was undertaken. Consecutive HIV-infected subjects presenting with skin complaints, who met criteria for ART initiation, were recruited at a Tanzanian Regional Dermatology Training Center. A single dermatologist evaluated all subjects; baseline skin biopsies were performed, and CD4(+) cell counts and plasma HIV RNA levels were measured. All subjects received a fixed-dose combination of stavudine, lamivudine, and nevirapine. A total of 100 subjects were enrolled; 86 subjects completed six months of follow-up. Median baseline CD4(+) cell counts and plasma HIV RNA levels were 120 cells/μl and 5.2 log10 copies/ml. The most common dermatologic condition was papular pruritic eruption (47%). The median baseline score on the Burn Scale was 38%. After six months, 10 subjects had achieved the complete resolution of skin abnormalities. In those without complete resolution, the median Burn Scale score improved to 7%. Five patients developed new eruptions by month 3, which in two cases were attributed to drug reactions. In the 86 subjects remaining on ART after six months, the median CD4(+) cell count had increased to 474 cells/μl, and plasma HIV RNA levels were <400 copies/ml in 85 (99%) subjects. Patients with HIV infection with skin complaints experienced marked clinical improvements following ART initiation.

Authors
Mavura, DR; Masenga, EJ; Minja, E; Grossmann, H; Crump, JA; Bartlett, JA
MLA Citation
Mavura, DR, Masenga, EJ, Minja, E, Grossmann, H, Crump, JA, and Bartlett, JA. "Initiation of antiretroviral therapy in HIV-infected adults with skin complaints in northern Tanzania." International journal of dermatology 54.1 (January 2015): 68-73.
Website
http://hdl.handle.net/10161/13770
PMID
25256912
Source
epmc
Published In
International Journal of Dermatology
Volume
54
Issue
1
Publish Date
2015
Start Page
68
End Page
73
DOI
10.1111/ijd.12563

IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes.

Despite comparable screening rates for precancerous lesions, higher incidence and mortality related to cervical cancer in minority women persists. Recent evidence suggests that minority women with precancerous cervical lesions harbor a wider range of human papillomavirus (HPV) genotypes, many of these distinct from HPV16/18, those most commonly found in Caucasian women. The goal of the analysis was to determine if inflammatory cytokines and chemokines varied by HPV 16/18 versus other genotypes in cervical cancer tissues from Tanzanian women.HPV genotypes and concentrations of chemokines and cytokines were measured from homogenized fresh tumor tissue of thirty-one women with invasive cervical cancer (ICC). Risk factors for cervical cancer including age, parity, hormonal contraceptive use and cigarette smoking were obtained by questionnaire. Generalized linear models were used to evaluate differences between chemokines/cytokine levels in women infected with HPV16/18 and those infected with other HPV genotypes.After adjusting for age, parity and hormonal contraceptives, IL-17 was found significantly more frequently in invasive cervical cancer samples of women infected with HPV16/18 compared to women infected with other HPV genotypes (p = 0.033). In contrast, higher levels for granular macrophage colony-stimulating factor (p = 0.004), IL-10 (p = 0.037), and IL-15 (p = 0.041) were found in ICC tissues of women infected with genotypes other than HPV16/18 when compared to those of women infected with HPV16/18.While the small sample size limits inference, our data suggest that infection with different HPV genotypes is associated with distinct pro-inflammatory cytokine expression profiles; whether this explains some of the racial differences observed in cervical cancer is still unclear. Future studies are needed to confirm these findings.

Authors
Vidal, AC; Skaar, D; Maguire, R; Dodor, S; Musselwhite, LW; Bartlett, JA; Oneko, O; Obure, J; Mlay, P; Murphy, SK; Hoyo, C
MLA Citation
Vidal, AC, Skaar, D, Maguire, R, Dodor, S, Musselwhite, LW, Bartlett, JA, Oneko, O, Obure, J, Mlay, P, Murphy, SK, and Hoyo, C. "IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes." Infectious agents and cancer 10 (January 2015): 10-.
Website
http://hdl.handle.net/10161/12657
PMID
25810759
Source
epmc
Published In
Infectious Agents and Cancer
Volume
10
Publish Date
2015
Start Page
10
DOI
10.1186/s13027-015-0005-1

Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV.

The integrase strand transfer inhibitors (INSTIs) are the newest antiretroviral class in the HIV treatment armamentarium. Dolutegravir (DTG) is the only second-generation INSTI with FDA approval (2013). It has potential advantages in comparison to first-generation INSTI's, including unboosted daily dosing, limited cross resistance with raltegravir and elvitegravir, and a high barrier to resistance. Clinical trials have evaluated DTG as a 50-mg daily dose in both treatment-naïve and treatment-experienced, INSTI-naïve participants. In those treatment-naïve participants with baseline viral load <100,000 copies/mL, DTG combined with abacavir and lamivudine was non-inferior and superior to fixed-dose combination emtricitabine/tenofovir/efavirenz. DTG was also superior to the protease inhibitor regimen darunavir/ritonavir in treatment-naïve participants regardless of baseline viral load. Among treatment-experienced patients naïve to INSTI, DTG (50 mg daily) demonstrated both non-inferiority and superiority when compared to the first-generation INSTI raltegravir (400 mg twice daily) regardless of the background regimen. No phenotypically significant DTG resistance has been demonstrated in INSTI-naïve participant trials. The VIKING trials evaluated DTG's ability to treat persons with HIV with prior INSTI exposure. VIKING demonstrated twice-daily DTG was more efficacious than daily dosing when treating participants receiving and failing first-generation INSTI regimens. DTG maintained potency against single mutations from any of the three major INSTI pathways (Y143, H155, Q148); however, the Q148 mutation with two or more additional mutations significantly reduced its potency. The long-acting formulation of DTG, GSK1265744LA, is the next innovation in this second-generation INSTI class, holding promise for the future of HIV prevention and treatment.

Authors
Dow, DE; Bartlett, JA
MLA Citation
Dow, DE, and Bartlett, JA. "Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV." Infectious diseases and therapy 3.2 (December 2014): 83-102. (Review)
PMID
25134686
Source
epmc
Published In
Infectious Diseases and Therapy
Volume
3
Issue
2
Publish Date
2014
Start Page
83
End Page
102
DOI
10.1007/s40121-014-0029-7

Association of first-line and second-line antiretroviral therapy adherence.

Adherence to first-line antiretroviral therapy (ART) may be an important indicator of adherence to second-line ART. Evaluating this relationship may be critical to identify patients at high risk for second-line failure, thereby exhausting their treatment options, and to intervene and improve patient outcomes.Adolescents and adults (n = 436) receiving second-line ART were administered standardized questionnaires that captured demographic characteristics and assessed adherence. Optimal and suboptimal cumulative adherence were defined as percentage adherence of ≥90% and <90%, respectively. Bivariable and multivariable binomial regression models were used to assess the prevalence of suboptimal adherence percentage by preswitch adherence status.A total of 134 of 436 (30.7%) participants reported suboptimal adherence to second-line ART. Among 322 participants who had suboptimal adherence to first-line ART, 117 (36.3%) had suboptimal adherence to second-line ART compared with 17 of 114 (14.9%) who had optimal adherence to first-line ART. Participants who had suboptimal adherence to first-line ART were more likely to have suboptimal adherence to second-line ART (adjusted prevalence ratio, 2.4; 95% confidence interval, 1.5-3.9).Adherence to first-line ART is an important predictor of adherence to second-line ART. Targeted interventions should be evaluated in patients with suboptimal adherence before switching into second-line therapy to improve their outcomes.

Authors
Ramadhani, HO; Bartlett, JA; Thielman, NM; Pence, BW; Kimani, SM; Maro, VP; Mwako, MS; Masaki, LJ; Mmbando, CE; Minja, MG; Lirhunde, ES; Miller, WC
MLA Citation
Ramadhani, HO, Bartlett, JA, Thielman, NM, Pence, BW, Kimani, SM, Maro, VP, Mwako, MS, Masaki, LJ, Mmbando, CE, Minja, MG, Lirhunde, ES, and Miller, WC. "Association of first-line and second-line antiretroviral therapy adherence." Open forum infectious diseases 1.2 (September 9, 2014): ofu079-.
PMID
25734147
Source
epmc
Published In
Open Forum Infectious Diseases
Volume
1
Issue
2
Publish Date
2014
Start Page
ofu079
DOI
10.1093/ofid/ofu079

Drug Susceptibility and Resistance Mutations After First-Line Failure in Resource Limited Settings

Authors
Wallis, CL; Aga, E; Ribaudo, H; Saravanan, S; Norton, M; Stevens, W; Kumarasamy, N; Bartlett, J; Katzenstein, D
MLA Citation
Wallis, CL, Aga, E, Ribaudo, H, Saravanan, S, Norton, M, Stevens, W, Kumarasamy, N, Bartlett, J, and Katzenstein, D. "Drug Susceptibility and Resistance Mutations After First-Line Failure in Resource Limited Settings." Clinical Infectious Diseases 59.5 (September 1, 2014): 706-715.
Source
crossref
Published In
Clinical Infectious Diseases
Volume
59
Issue
5
Publish Date
2014
Start Page
706
End Page
715
DOI
10.1093/cid/ciu314

Modernizing and transforming medical education at the Kilimanjaro Christian Medical University College.

The Kilimanjaro Christian Medical University (KCMU) College and the Medical Education Partnership Initiative (MEPI) are addressing the crisis in Tanzanian health care manpower by modernizing the college's medical education with new tools and techniques. With a $10 million MEPI grant and the participation of its partner, Duke University, KCMU is harnessing the power of information technology (IT) to upgrade tools for students and faculty. Initiatives in eLearning have included bringing fiber-optic connectivity to the campus, offering campus-wide wireless access, opening student and faculty computer laboratories, and providing computer tablets to all incoming medical students. Beyond IT, the college is also offering wet laboratory instruction for hands-on diagnostic skills, team-based learning, and clinical skills workshops. In addition, modern teaching tools and techniques address the challenges posed by increasing numbers of students. To provide incentives for instructors, a performance-based compensation plan and teaching awards have been established. Also for faculty, IT tools and training have been made available, and a medical education course management system is now being widely employed. Student and faculty responses have been favorable, and the rapid uptake of these interventions by students, faculty, and the college's administration suggests that the KCMU College MEPI approach has addressed unmet needs. This enabling environment has transformed the culture of learning and teaching at KCMU College, where a path to sustainability is now being pursued.

Authors
Lisasi, E; Kulanga, A; Muiruri, C; Killewo, L; Fadhili, N; Mimano, L; Kapanda, G; Tibyampansha, D; Ibrahim, G; Nyindo, M; Mteta, K; Kessi, E; Ntabaye, M; Bartlett, J
MLA Citation
Lisasi, E, Kulanga, A, Muiruri, C, Killewo, L, Fadhili, N, Mimano, L, Kapanda, G, Tibyampansha, D, Ibrahim, G, Nyindo, M, Mteta, K, Kessi, E, Ntabaye, M, and Bartlett, J. "Modernizing and transforming medical education at the Kilimanjaro Christian Medical University College." Academic medicine : journal of the Association of American Medical Colleges 89.8 Suppl (August 2014): S60-S64.
PMID
25072581
Source
epmc
Published In
Academic Medicine
Volume
89
Issue
8 Suppl
Publish Date
2014
Start Page
S60
End Page
S64
DOI
10.1097/acm.0000000000000327

Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.

Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment.We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality.Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function.We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.

Authors
Bartz, S; Mody, A; Hornik, C; Bain, J; Muehlbauer, M; Kiyimba, T; Kiboneka, E; Stevens, R; Bartlett, J; St Peter, JV; Newgard, CB; Freemark, M
MLA Citation
Bartz, S, Mody, A, Hornik, C, Bain, J, Muehlbauer, M, Kiyimba, T, Kiboneka, E, Stevens, R, Bartlett, J, St Peter, JV, Newgard, CB, and Freemark, M. "Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality." The Journal of clinical endocrinology and metabolism 99.6 (June 2014): 2128-2137.
PMID
24606092
Source
epmc
Published In
Journal of Clinical Endocrinology and Metabolism
Volume
99
Issue
6
Publish Date
2014
Start Page
2128
End Page
2137
DOI
10.1210/jc.2013-4018

Introduction of team-based learning (TBL) at Kilimanjaro Christian Medical University College: experience with the ectoparasites module.

Contemporary teaching in sub-Saharan African medical schools is largely through didactic and problem-based approaches. These schools face challenges from burgeoning student numbers, severe faculty shortages, faculty without instruction in teaching methods and severe infrastructure inadequacies. Team-based learning (TBL) is a pedagogy which may be attractive because it spares faculty time. TBL was piloted in a module on ectoparasites at the Kilimanjaro Christian Medical University College (KCMU Co.).TBL orientation began six weeks before starting the module. Students were issued background readings and individual and group readiness assessment tests, followed by module application, discussion and evaluation. At completion, student perceptions of TBL were assessed using a 5-point Likert scale evaluating six domains, with a score of 5 being most favourable. Strength of consensus measures (sCns) was applied. Final examination scores were compiled for 2011 (didactic) and 2012 (TBL).About 158 students participated in the module. The mean student scores across the six domains ranged from 4.2 to 4.5, with a high degree of consensus (range 85-90%). The final examination scores improved between 2011 and 2012.KCMU Co. student perceptions of TBL were very positive, and final exam grades improved. These observations suggest future promise for TBL applications at KCMU Co. and potentially other schools.

Authors
Nyindo, M; Kitau, J; Lisasi, E; Kapanda, G; Matowo, J; Francis, P; Bartlett, J
MLA Citation
Nyindo, M, Kitau, J, Lisasi, E, Kapanda, G, Matowo, J, Francis, P, and Bartlett, J. "Introduction of team-based learning (TBL) at Kilimanjaro Christian Medical University College: experience with the ectoparasites module." Medical teacher 36.4 (April 2014): 308-313.
PMID
24491164
Source
epmc
Published In
Medical Teacher (Informa)
Volume
36
Issue
4
Publish Date
2014
Start Page
308
End Page
313
DOI
10.3109/0142159x.2013.876490

PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer

Introduction: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. Materials and methods: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. Results: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. Conclusions: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk. © 2013 The Author(s).

Authors
Vidal, AC; Henry, NM; Murphy, SK; Oneko, O; Nye, M; Bartlett, JA; Overcash, F; Huang, Z; Wang, F; Mlay, P; Obure, J; Smith, J; Vasquez, B; Swai, B; Hernandez, B; Hoyo, C
MLA Citation
Vidal, AC, Henry, NM, Murphy, SK, Oneko, O, Nye, M, Bartlett, JA, Overcash, F, Huang, Z, Wang, F, Mlay, P, Obure, J, Smith, J, Vasquez, B, Swai, B, Hernandez, B, and Hoyo, C. "PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer." Clinical and Translational Oncology 16.3 (March 1, 2014): 266-272.
Source
scopus
Published In
Clinical and Translational Oncology
Volume
16
Issue
3
Publish Date
2014
Start Page
266
End Page
272
DOI
10.1007/s12094-013-1067-4

PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer.

INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.

Authors
Vidal, AC; Henry, NM; Murphy, SK; Oneko, O; Nye, M; Bartlett, JA; Overcash, F; Huang, Z; Wang, F; Mlay, P; Obure, J; Smith, J; Vasquez, B; Swai, B; Hernandez, B; Hoyo, C
MLA Citation
Vidal, AC, Henry, NM, Murphy, SK, Oneko, O, Nye, M, Bartlett, JA, Overcash, F, Huang, Z, Wang, F, Mlay, P, Obure, J, Smith, J, Vasquez, B, Swai, B, Hernandez, B, and Hoyo, C. "PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer." Clin Transl Oncol 16.3 (March 2014): 266-272.
PMID
23775149
Source
pubmed
Published In
Clinical and Translational Oncology
Volume
16
Issue
3
Publish Date
2014
Start Page
266
End Page
272
DOI
10.1007/s12094-013-1067-4

A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania.

Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis.Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis).Seventy participants were randomized to standard (n = 37, 53%) or intensive (n = 33, 47%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04).Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.

Authors
Reddy, EA; Njau, BN; Morpeth, SC; Lancaster, KE; Tribble, AC; Maro, VP; Msuya, LJ; Morrissey, AB; Kibiki, GS; Thielman, NM; Cunningham, CK; Schimana, W; Shao, JF; Chow, S-C; Stout, JE; Crump, JA; Bartlett, JA; Hamilton, CD
MLA Citation
Reddy, EA, Njau, BN, Morpeth, SC, Lancaster, KE, Tribble, AC, Maro, VP, Msuya, LJ, Morrissey, AB, Kibiki, GS, Thielman, NM, Cunningham, CK, Schimana, W, Shao, JF, Chow, S-C, Stout, JE, Crump, JA, Bartlett, JA, and Hamilton, CD. "A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania." BMC infectious diseases 14 (February 20, 2014): 89-.
Website
http://hdl.handle.net/10161/13774
PMID
24552306
Source
epmc
Published In
BMC Infectious Diseases
Volume
14
Publish Date
2014
Start Page
89
DOI
10.1186/1471-2334-14-89

A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania

Background: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. Methods: Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). Results: Seventy participants were randomized to standard (n = 37, 53%) or intensive (n = 33, 47%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). Conclusions: Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve. © 2014 Reddy et al.; licensee BioMed Central Ltd.

Authors
Reddy, EA; Njau, BN; Morpeth, SC; Lancaster, KE; Tribble, AC; Maro, VP; Msuya, LJ; Morrissey, AB; Kibiki, GS; Thielman, NM; Cunningham, CK; Schimana, W; Shao, JF; Chow, SC; Stout, JE; Crump, JA; Bartlett, JA; Hamilton, CD
MLA Citation
Reddy, EA, Njau, BN, Morpeth, SC, Lancaster, KE, Tribble, AC, Maro, VP, Msuya, LJ, Morrissey, AB, Kibiki, GS, Thielman, NM, Cunningham, CK, Schimana, W, Shao, JF, Chow, SC, Stout, JE, Crump, JA, Bartlett, JA, and Hamilton, CD. "A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania." BMC Infectious Diseases 14.1 (February 20, 2014).
Source
scopus
Published In
BMC Infectious Diseases
Volume
14
Issue
1
Publish Date
2014
DOI
10.1186/1471-2334-14-89

Progress in the prevention of mother to child transmission of HIV in three regions of Tanzania: a retrospective analysis.

Mother to child transmission (MTCT) of HIV-1 remains an important problem in sub-Saharan Africa where most new pediatric HIV-1 infections occur. Early infant diagnosis of HIV-1 using dried blood spot (DBS) PCR among exposed infants provides an opportunity to assess current MTCT rates.We conducted a retrospective data analysis on mother-infant pairs from all PMTCT programs in three regions of northern Tanzania to determine MTCT rates from 2008-2010. Records of 3,016 mother-infant pairs were assessed to determine early transmission among HIV-exposed infants in the first 75 days of life.Of 2,266 evaluable infants in our cohort, 143 had a positive DBS PCR result at ≤ 75 days of life, for an overall transmission rate of 6.3%. Transmission decreased substantially over the period of study as more effective regimens became available. Transmission rates were tightly correlated to maternal regimen: 14.9% (9.5, 20.3) of infants became infected when women received no therapy; 8.8% (6.9, 10.7) and 3.6% (2.4, 4.8) became infected when women received single-dose nevirapine (sdNVP) or combination prophylaxis, respectively; the lowest MTCT rates occurred when women were on HAART, with 2.1% transmission (0.3, 3.9). Treatment regimens changed dramatically over the study period, with an increase in combination prophylaxis and a decrease in the use of sdNVP. Uptake of DBS PCR more than tripled over the period of study for the three regions surveyed.Our study demonstrates significant reductions in MTCT of HIV-1 in three regions of Tanzania coincident with increased use of more effective PMTCT interventions. The changes we demonstrate for the period of 2008-2010 occurred prior to major changes in WHO PMTCT guidelines.

Authors
Buchanan, AM; Dow, DE; Massambu, CG; Nyombi, B; Shayo, A; Musoke, R; Feng, S; Bartlett, JA; Cunningham, CK; Schimana, W
MLA Citation
Buchanan, AM, Dow, DE, Massambu, CG, Nyombi, B, Shayo, A, Musoke, R, Feng, S, Bartlett, JA, Cunningham, CK, and Schimana, W. "Progress in the prevention of mother to child transmission of HIV in three regions of Tanzania: a retrospective analysis." PloS one 9.2 (January 2014): e88679-.
PMID
24551134
Source
epmc
Published In
PloS one
Volume
9
Issue
2
Publish Date
2014
Start Page
e88679
DOI
10.1371/journal.pone.0088679

Sustainability of cancer registration in the Kilimanjaro Region of Tanzania--a qualitative assessment.

The projected cancer burden in Africa demands a comprehensive surveillance strategy. Kilimanjaro Christian Medical Centre (KCMC) is developing a population-based cancer registry, and understanding stakeholders' perceptions of factors impacting cancer registration sustainability is critical to its long-term success. We conducted 11 semi-structured qualitative interviews with clinicians and administrators. Interviews were double-coded and evaluated for predetermined and emerging themes. Nearly half (45%) of participants discussed change commitment, stating that the cancer registry would benefit KCMC and that they were committed to it. However, change efficacy was low - participants were not confident in their shared ability to sustain the registry. Most participants (73%) discussed the importance of resource availability and administration support. Several themes emerged across interviews: (i) lack of cancer registry awareness, (ii) ambiguity about its purpose, (iii) the importance of training, (iv) the importance of outcome data, and (v) the importance of international partners. These findings may facilitate cancer registry development and sustainability in similar settings.

Authors
Zullig, LL; Vanderburg, SB; Muiruri, C; Abernethy, A; Weiner, BJ; Bartlett, J
MLA Citation
Zullig, LL, Vanderburg, SB, Muiruri, C, Abernethy, A, Weiner, BJ, and Bartlett, J. "Sustainability of cancer registration in the Kilimanjaro Region of Tanzania--a qualitative assessment." World health & population 15.1 (January 2014): 21-30.
PMID
24702763
Source
epmc
Published In
Journal of World Health and Population
Volume
15
Issue
1
Publish Date
2014
Start Page
21
End Page
30
DOI
10.12927/whp.2014.23721

Effects of HIV infection on the metabolic and hormonal status of children with severe acute malnutrition.

HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood.We conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy.At admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score -4.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR = 8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality.Our findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children.

Authors
Mody, A; Bartz, S; Hornik, CP; Kiyimba, T; Bain, J; Muehlbauer, M; Kiboneka, E; Stevens, R; St Peter, JV; Newgard, CB; Bartlett, J; Freemark, M
MLA Citation
Mody, A, Bartz, S, Hornik, CP, Kiyimba, T, Bain, J, Muehlbauer, M, Kiboneka, E, Stevens, R, St Peter, JV, Newgard, CB, Bartlett, J, and Freemark, M. "Effects of HIV infection on the metabolic and hormonal status of children with severe acute malnutrition." PloS one 9.7 (January 2014): e102233-.
PMID
25050734
Source
epmc
Published In
PloS one
Volume
9
Issue
7
Publish Date
2014
Start Page
e102233
DOI
10.1371/journal.pone.0102233

Integrating Routine HIV Screening Into a Primary Care Setting in Rural North Carolina

Blacks living in the southern United States are disproportionately affected by HIV infection. Identifying and treating those who are infected is an important strategy for reducing HIV transmission. A model for integrating rapid HIV screening into community health centers was modified and used to guide implementation of a testing program in a primary care setting in a small North Carolina town serving a rural Black population. Anonymous surveys were completed by 138 adults who were offered an HIV test; of these, 61% were female and 89.9% were Black. One hundred patients (72%) accepted the test. Among those Black survey respondents who accepted an offer of testing, 58% were women. The most common reason for declining an HIV test was lack of perceived risk; younger patients were more likely to get tested. Implementation of the testing model posed challenges with time, data collection, and patient flow. © 2014 Association of Nurses in AIDS Care.

Authors
Harmon, JL; Collins-Ogle, M; Bartlett, JA; Thompson, J; Barroso, J
MLA Citation
Harmon, JL, Collins-Ogle, M, Bartlett, JA, Thompson, J, and Barroso, J. "Integrating Routine HIV Screening Into a Primary Care Setting in Rural North Carolina." Journal of the Association of Nurses in AIDS Care 25.1 (2014): 70-82.
Source
scival
Published In
Journal of the Association of Nurses in AIDS Care
Volume
25
Issue
1
Publish Date
2014
Start Page
70
End Page
82
DOI
10.1016/j.jana.2013.01.001

PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer

Authors
Vidal, AC; Henry, NM; Murphy, SK; Oneko, O; Nye, M; Bartlett, JA; Overcash, F; Huang, Z; Wang, F; Mlay, P; Obure, J; Smith, J; Vasquez, B; Swai, B; Hernandez, B; Hoyo, C
MLA Citation
Vidal, AC, Henry, NM, Murphy, SK, Oneko, O, Nye, M, Bartlett, JA, Overcash, F, Huang, Z, Wang, F, Mlay, P, Obure, J, Smith, J, Vasquez, B, Swai, B, Hernandez, B, and Hoyo, C. "PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer." Clinical and Translational Oncology 16.3 (2014): 266-272.
Source
scopus
Published In
Clinical and Translational Oncology
Volume
16
Issue
3
Publish Date
2014
Start Page
266
End Page
272

Prognosis and delay of diagnosis among Kaposi’s sarcoma patients in Uganda: a cross-sectional study

Authors
De Boer, C; Niyonzima, N; Orem, J; Bartlett, J; Zafar, S
MLA Citation
De Boer, C, Niyonzima, N, Orem, J, Bartlett, J, and Zafar, S. "Prognosis and delay of diagnosis among Kaposi’s sarcoma patients in Uganda: a cross-sectional study." Infectious Agents and Cancer 9.1 (2014): 17-17.
Source
crossref
Published In
Infectious Agents and Cancer
Volume
9
Issue
1
Publish Date
2014
Start Page
17
End Page
17
DOI
10.1186/1750-9378-9-17

Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania.

AIM: To describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting. MATERIALS AND METHODS: Febrile patients were enrolled in Moshi, Tanzania, and chest radiographs were evaluated by radiologists in Tanzania and the United States. Radiologists were blinded to the results of extensive laboratory evaluations to determine the cause of fever. RESULTS: Of 870 febrile patients, 515 (59.2%) had a chest radiograph available; including 268 (66.5%) of the adolescents and adults, the remainder were infants and children. One hundred and nineteen (44.4%) adults and 51 (20.6%) children were human immunodeficiency virus (HIV)-infected. Among adults, radiographic abnormalities were present in 139 (51.9%), including 77 (28.7%) with homogeneous and heterogeneous lung opacities, 26 (9.7%) with lung nodules, 25 (9.3%) with pleural effusion, 23 (8.6%) with cardiomegaly, and 13 (4.9%) with lymphadenopathy. Among children, radiographic abnormalities were present in 87 (35.2%), including 76 (30.8%) with homogeneous and heterogeneous lung opacities and six (2.4%) with lymphadenopathy. Among adolescents and adults, the presence of opacities was predictive of Streptococcus pneumoniae and Coxiella burnetii, whereas the presence of pulmonary nodules was predictive of Histoplasma capsulatum and Cryptococcus neoformans. CONCLUSIONS: Chest radiograph abnormalities among febrile inpatients are common in northern Tanzania. Chest radiography is a useful adjunct for establishing an aetiologic diagnosis of febrile illness and may provide useful information for patient management, in particular for pneumococcal disease, Q fever, and fungal infections.

Authors
Fiorillo, SP; Diefenthal, HC; Goodman, PC; Ramadhani, HO; Njau, BN; Morrissey, AB; Maro, VP; Saganda, W; Kinabo, GD; Mwako, MS; Bartlett, JA; Crump, JA
MLA Citation
Fiorillo, SP, Diefenthal, HC, Goodman, PC, Ramadhani, HO, Njau, BN, Morrissey, AB, Maro, VP, Saganda, W, Kinabo, GD, Mwako, MS, Bartlett, JA, and Crump, JA. "Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania." Clin Radiol 68.10 (October 2013): 1039-1046.
PMID
23809268
Source
pubmed
Published In
Clinical Radiology
Volume
68
Issue
10
Publish Date
2013
Start Page
1039
End Page
1046
DOI
10.1016/j.crad.2013.05.002

Lack of protease inhibitor resistance following treatment failure--too good to be true?

A 29-year-old man with recently diagnosed HIV infection and a CD4 cell count of 225/mm³ began treatment with atazanavir (300 mg), ritonavir (100 mg), emtricitabine (200 mg), and tenofovir (300 mg) daily. For 18 months, he was treatment adherent and his plasma HIV RNA level was below the limit of detection. He then began a relationship with a new partner, who introduced him to methamphetamines. His medication adherence became erratic, and he missed appointments in clinic. Eventually. he was hospitalized for rehabilitation, and he resumed taking his medications on schedule. Following his discharge, he was found to have a plasma HIV RNA level of 11,400 copies/ml. Genotypic resistance testing revealed only an M184V mutation associated with emtricitabine resistance. A decision regarding his next treatment regimen needs to be made.

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "Lack of protease inhibitor resistance following treatment failure--too good to be true?." J Clin Invest 123.9 (September 2013): 3704-3705.
PMID
23979153
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
123
Issue
9
Publish Date
2013
Start Page
3704
End Page
3705
DOI
10.1172/JCI71784

Associations between HLA-DRB1*0102, HLA-B*5801, and hepatotoxicity during initiation of nevirapine-containing regimens in South Africa.

Authors
Phillips, E; Bartlett, JA; Sanne, I; Lederman, MM; Hinkle, J; Rousseau, F; Dunn, D; Pavlos, R; James, I; Mallal, SA; Haas, DW
MLA Citation
Phillips, E, Bartlett, JA, Sanne, I, Lederman, MM, Hinkle, J, Rousseau, F, Dunn, D, Pavlos, R, James, I, Mallal, SA, and Haas, DW. "Associations between HLA-DRB1*0102, HLA-B*5801, and hepatotoxicity during initiation of nevirapine-containing regimens in South Africa." J Acquir Immune Defic Syndr 62.2 (February 1, 2013): e55-e57. (Letter)
PMID
23328091
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
62
Issue
2
Publish Date
2013
Start Page
e55
End Page
e57
DOI
10.1097/QAI.0b013e31827ca50f

Associations between methylation of paternally expressed gene 3 (PEG3), cervical intraepithelial neoplasia and invasive cervical cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress.

Authors
Nye, MD; Hoyo, C; Huang, Z; Vidal, AC; Wang, F; Overcash, F; Smith, JS; Vasquez, B; Hernandez, B; Swai, B; Oneko, O; Mlay, P; Obure, J; Gammon, MD; Bartlett, JA; Murphy, SK
MLA Citation
Nye, MD, Hoyo, C, Huang, Z, Vidal, AC, Wang, F, Overcash, F, Smith, JS, Vasquez, B, Hernandez, B, Swai, B, Oneko, O, Mlay, P, Obure, J, Gammon, MD, Bartlett, JA, and Murphy, SK. "Associations between methylation of paternally expressed gene 3 (PEG3), cervical intraepithelial neoplasia and invasive cervical cancer." PLoS One 8.2 (2013): e56325-.
PMID
23418553
Source
pubmed
Published In
PloS one
Volume
8
Issue
2
Publish Date
2013
Start Page
e56325
DOI
10.1371/journal.pone.0056325

Integrating Routine HIV Screening Into a Primary Care Setting in Rural North Carolina

Blacks living in the southern United States are disproportionately affected by HIV infection. Identifying and treating those who are infected is an important strategy for reducing HIV transmission. A model for integrating rapid HIV screening into community health centers was modified and used to guide implementation of a testing program in a primary care setting in a small North Carolina town serving a rural Black population. Anonymous surveys were completed by 138 adults who were offered an HIV test; of these, 61% were female and 89.9% were Black. One hundred patients (72%) accepted the test. Among those Black survey respondents who accepted an offer of testing, 58% were women. The most common reason for declining an HIV test was lack of perceived risk; younger patients were more likely to get tested. Implementation of the testing model posed challenges with time, data collection, and patient flow. © 2013 Association of Nurses in AIDS Care.

Authors
Harmon, JL; Collins-Ogle, M; Bartlett, JA; Thompson, J; Barroso, J
MLA Citation
Harmon, JL, Collins-Ogle, M, Bartlett, JA, Thompson, J, and Barroso, J. "Integrating Routine HIV Screening Into a Primary Care Setting in Rural North Carolina." Journal of the Association of Nurses in AIDS Care (2013).
PMID
23582578
Source
scival
Published In
Journal of the Association of Nurses in AIDS Care
Publish Date
2013
DOI
10.1016/j.jana.2013.01.001

Cancer registration needs assessment at a tertiary medical centre in Kilimanjaro, Tanzania.

Cancer burden is increasing in Africa more than in any other continent, but population-based tracking of cancer incidence is incomplete. Cancer registries can improve understanding of cancer incidence. To assess organizational readiness to sustain registry development, we conducted a survey assessing change efficacy, resource availability and change commitment at the Kilimanjaro Christian Medical Centre (KCMC), an academic hospital in Moshi, Tanzania. Fifty-two surveys were returned (80% response rate). There was strong reliability among change efficacy and commitment survey items, with Cronbach's alphas of 0.93 and 0.77, respectively. Clinicians, nurses and administrators conveyed similar responses regarding change efficacy. Clinicians had similar responses for change commitment. Echoing opinion in many low- and middle-income countries, approximately one-third of respondents indicated there were no funds to maintain the registry, and funds were not obtainable. For most resources, respondents felt that resources were sufficient or attainable. Respondents were generally confident and committed to registry implementation. Lessons learned at KCMC may be more broadly relevant.

Authors
Zullig, LL; Muiruri, C; Abernethy, A; Weiner, BJ; Bartlett, J; Oneko, O; Zafar, SY
MLA Citation
Zullig, LL, Muiruri, C, Abernethy, A, Weiner, BJ, Bartlett, J, Oneko, O, and Zafar, SY. "Cancer registration needs assessment at a tertiary medical centre in Kilimanjaro, Tanzania." World Health Popul 14.2 (2013): 12-23.
PMID
23713208
Source
pubmed
Published In
World Health Popul
Volume
14
Issue
2
Publish Date
2013
Start Page
12
End Page
23

Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study.

INTRODUCTION: The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. METHODS AND FINDINGS: We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. CONCLUSIONS: Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.

Authors
Crump, JA; Morrissey, AB; Nicholson, WL; Massung, RF; Stoddard, RA; Galloway, RL; Ooi, EE; Maro, VP; Saganda, W; Kinabo, GD; Muiruri, C; Bartlett, JA
MLA Citation
Crump, JA, Morrissey, AB, Nicholson, WL, Massung, RF, Stoddard, RA, Galloway, RL, Ooi, EE, Maro, VP, Saganda, W, Kinabo, GD, Muiruri, C, and Bartlett, JA. "Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study. (Published online)" PLoS Negl Trop Dis 7.7 (2013): e2324-.
Website
http://hdl.handle.net/10161/13779
PMID
23875053
Source
pubmed
Published In
PLoS neglected tropical diseases
Volume
7
Issue
7
Publish Date
2013
Start Page
e2324
DOI
10.1371/journal.pntd.0002324

Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania

Aim To describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting. Materials and methods Febrile patients were enrolled in Moshi, Tanzania, and chest radiographs were evaluated by radiologists in Tanzania and the United States. Radiologists were blinded to the results of extensive laboratory evaluations to determine the cause of fever. Results Of 870 febrile patients, 515 (59.2%) had a chest radiograph available; including 268 (66.5%) of the adolescents and adults, the remainder were infants and children. One hundred and nineteen (44.4%) adults and 51 (20.6%) children were human immunodeficiency virus (HIV)-infected. Among adults, radiographic abnormalities were present in 139 (51.9%), including 77 (28.7%) with homogeneous and heterogeneous lung opacities, 26 (9.7%) with lung nodules, 25 (9.3%) with pleural effusion, 23 (8.6%) with cardiomegaly, and 13 (4.9%) with lymphadenopathy. Among children, radiographic abnormalities were present in 87 (35.2%), including 76 (30.8%) with homogeneous and heterogeneous lung opacities and six (2.4%) with lymphadenopathy. Among adolescents and adults, the presence of opacities was predictive of Streptococcus pneumoniae and Coxiella burnetii, whereas the presence of pulmonary nodules was predictive of Histoplasma capsulatum and Cryptococcus neoformans. Conclusions Chest radiograph abnormalities among febrile inpatients are common in northern Tanzania. Chest radiography is a useful adjunct for establishing an aetiologic diagnosis of febrile illness and may provide useful information for patient management, in particular for pneumococcal disease, Q fever, and fungal infections. © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Authors
Fiorillo, SP; Diefenthal, HC; Goodman, PC; Ramadhani, HO; Njau, BN; Morrissey, AB; Maro, VP; Saganda, W; Kinabo, GD; Mwako, MS; Bartlett, JA; Crump, JA
MLA Citation
Fiorillo, SP, Diefenthal, HC, Goodman, PC, Ramadhani, HO, Njau, BN, Morrissey, AB, Maro, VP, Saganda, W, Kinabo, GD, Mwako, MS, Bartlett, JA, and Crump, JA. "Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania." Clinical Radiology 68.10 (2013): 1039-1046.
Source
scival
Published In
Clinical Radiology
Volume
68
Issue
10
Publish Date
2013
Start Page
1039
End Page
1046
DOI
10.1016/j.crad.2013.05.002

Brucellosis among hospitalized febrile patients in northern Tanzania.

Acute and convalescent serum samples were collected from febrile inpatients identified at two hospitals in Moshi, Tanzania. Confirmed brucellosis was defined as a positive blood culture or a ≥ 4-fold increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer ≥ 160. Among 870 participants enrolled in the study, 455 (52.3%) had paired sera available. Of these, 16 (3.5%) met criteria for confirmed brucellosis. Of 830 participants with ≥ 1 serum sample, 4 (0.5%) met criteria for probable brucellosis. Brucellosis was associated with increased median age (P = 0.024), leukopenia (odds ratio [OR] 7.8, P = 0.005), thrombocytopenia (OR 3.9, P = 0.018), and evidence of other zoonoses (OR 3.2, P = 0.026). Brucellosis was never diagnosed clinically, and although all participants with brucellosis received antibacterials or antimalarials in the hospital, no participant received standard brucellosis treatment. Brucellosis is an underdiagnosed and untreated cause of febrile disease among hospitalized adult and pediatric patients in northern Tanzania.

Authors
Bouley, AJ; Biggs, HM; Stoddard, RA; Morrissey, AB; Bartlett, JA; Afwamba, IA; Maro, VP; Kinabo, GD; Saganda, W; Cleaveland, S; Crump, JA
MLA Citation
Bouley, AJ, Biggs, HM, Stoddard, RA, Morrissey, AB, Bartlett, JA, Afwamba, IA, Maro, VP, Kinabo, GD, Saganda, W, Cleaveland, S, and Crump, JA. "Brucellosis among hospitalized febrile patients in northern Tanzania." Am J Trop Med Hyg 87.6 (December 2012): 1105-1111.
Website
http://hdl.handle.net/10161/13793
PMID
23091197
Source
pubmed
Published In
American Journal of Tropical Medicine and Hygiene
Volume
87
Issue
6
Publish Date
2012
Start Page
1105
End Page
1111
DOI
10.4269/ajtmh.2012.12-0327

Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings.

OBJECTIVE: To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs). DESIGN: An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000  copies/ml. METHODS: Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100  mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r. RESULTS: Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400  copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40  copies/ml and 30 had levels 40-200  copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400  copies/ml. CONCLUSION: In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.

Authors
Bartlett, JA; Ribaudo, HJ; Wallis, CL; Aga, E; Katzenstein, DA; Stevens, WS; Norton, MR; Klingman, KL; Hosseinipour, MC; Crump, JA; Supparatpinyo, K; Badal-Faesen, S; Kallungal, BA; Kumarasamy, N
MLA Citation
Bartlett, JA, Ribaudo, HJ, Wallis, CL, Aga, E, Katzenstein, DA, Stevens, WS, Norton, MR, Klingman, KL, Hosseinipour, MC, Crump, JA, Supparatpinyo, K, Badal-Faesen, S, Kallungal, BA, and Kumarasamy, N. "Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings." AIDS 26.11 (July 17, 2012): 1345-1354.
Website
http://hdl.handle.net/10161/13791
PMID
22441252
Source
pubmed
Published In
AIDS
Volume
26
Issue
11
Publish Date
2012
Start Page
1345
End Page
1354
DOI
10.1097/QAD.0b013e328353b066

Bacteremic disseminated tuberculosis in sub-saharan Africa: a prospective cohort study.

BACKGROUND: Disseminated tuberculosis is a major health problem in countries where generalized human immunodeficiency virus (HIV) infection epidemics coincide with high tuberculosis incidence rates; data are limited on patient outcomes beyond the inpatient period. METHODS: We enrolled consecutive eligible febrile inpatients in Moshi, Tanzania, from 10 March 2006 through 28 August 2010; those with Mycobacterium tuberculosis bacteremia were followed up monthly for 12 months. Survival, predictors of bacteremic disseminated tuberculosis, and predictors of death were assessed. Antiretroviral therapy (ART) and tuberculosis treatment were provided. RESULTS: A total of 508 participants were enrolled; 29 (5.7%) had M. tuberculosis isolated by blood culture. The median age of all study participants was 37.4 years (range, 13.6-104.8 years). Cough lasting >1 month (odds ratio [OR], 13.5; P< .001), fever lasting >1 month (OR, 7.8; P = .001), weight loss of >10% (OR, 10.0; P = .001), lymphadenopathy (OR 6.8; P = .002), HIV infection (OR, undefined; P < .001), and lower CD4 cell count and total lymphocyte count were associated with bacteremic disseminated tuberculosis. Fifty percent of participants with M. tuberculosis bacteremia died within 36 days of enrollment. Lower CD4 cell count (OR, 0.88; P = .049) and lower total lymphocyte count (OR, 0.76; P = .050) were associated with death. Magnitude of mycobacteremia tended to be higher among those with lower CD4 cell counts, but did not predict death. CONCLUSIONS: In the era of free ART and access to tuberculosis treatment, almost one half of patients with M. tuberculosis bacteremia may die within a month of hospitalization. Simple clinical assessments can help to identify those with the condition. Advanced immunosuppression predicts death. Efforts should focus on early diagnosis and treatment of HIV infection, tuberculosis, and disseminated disease.

Authors
Crump, JA; Ramadhani, HO; Morrissey, AB; Saganda, W; Mwako, MS; Yang, L-Y; Chow, S-C; Njau, BN; Mushi, GS; Maro, VP; Reller, LB; Bartlett, JA
MLA Citation
Crump, JA, Ramadhani, HO, Morrissey, AB, Saganda, W, Mwako, MS, Yang, L-Y, Chow, S-C, Njau, BN, Mushi, GS, Maro, VP, Reller, LB, and Bartlett, JA. "Bacteremic disseminated tuberculosis in sub-saharan Africa: a prospective cohort study." Clin Infect Dis 55.2 (July 2012): 242-250.
Website
http://hdl.handle.net/10161/13794
PMID
22511551
Source
pubmed
Published In
Clinical Infectious Diseases
Volume
55
Issue
2
Publish Date
2012
Start Page
242
End Page
250
DOI
10.1093/cid/cis409

Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania.

Consecutive febrile admissions were enrolled at two hospitals in Moshi, Tanzania. Confirmed acute Chikungunya virus (CHIKV), Dengue virus (DENV), and flavivirus infection were defined as a positive polymerase chain reaction (PCR) result. Presumptive acute DENV infection was defined as a positive anti-DENV immunoglobulin M (IgM) enzyme-linked immunsorbent assay (ELISA) result, and prior flavivirus exposure was defined as a positive anti-DENV IgG ELISA result. Among 870 participants, PCR testing was performed on 700 (80.5%). Of these, 55 (7.9%) had confirmed acute CHIKV infection, whereas no participants had confirmed acute DENV or flavivirus infection. Anti-DENV IgM serologic testing was performed for 747 (85.9%) participants, and of these 71 (9.5%) had presumptive acute DENV infection. Anti-DENV IgG serologic testing was performed for 751 (86.3%) participants, and of these 80 (10.7%) had prior flavivirus exposure. CHIKV infection was more common among infants and children than adults and adolescents (odds ratio [OR] 1.9, P = 0.026) and among HIV-infected patients with severe immunosuppression (OR 10.5, P = 0.007). CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania. DENV or other closely related flaviviruses are likely also circulating.

Authors
Hertz, JT; Munishi, OM; Ooi, EE; Howe, S; Lim, WY; Chow, A; Morrissey, AB; Bartlett, JA; Onyango, JJ; Maro, VP; Kinabo, GD; Saganda, W; Gubler, DJ; Crump, JA
MLA Citation
Hertz, JT, Munishi, OM, Ooi, EE, Howe, S, Lim, WY, Chow, A, Morrissey, AB, Bartlett, JA, Onyango, JJ, Maro, VP, Kinabo, GD, Saganda, W, Gubler, DJ, and Crump, JA. "Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania." Am J Trop Med Hyg 86.1 (January 2012): 171-177.
Website
http://hdl.handle.net/10161/6330
PMID
22232469
Source
pubmed
Published In
American Journal of Tropical Medicine and Hygiene
Volume
86
Issue
1
Publish Date
2012
Start Page
171
End Page
177
DOI
10.4269/ajtmh.2012.11-0393

Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women.

BACKGROUND: Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection. RESULTS: 79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases. CONCLUSIONS: In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes.

Authors
Vidal, AC; Murphy, SK; Hernandez, BY; Vasquez, B; Bartlett, JA; Oneko, O; Mlay, P; Obure, J; Overcash, F; Smith, JS; van der Kolk, M; Hoyo, C
MLA Citation
Vidal, AC, Murphy, SK, Hernandez, BY, Vasquez, B, Bartlett, JA, Oneko, O, Mlay, P, Obure, J, Overcash, F, Smith, JS, van der Kolk, M, and Hoyo, C. "Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women. (Published online)" Infect Agent Cancer 6.1 (November 14, 2011): 20-.
Website
http://hdl.handle.net/10161/5939
PMID
22081870
Source
pubmed
Published In
Infectious Agents and Cancer
Volume
6
Issue
1
Publish Date
2011
Start Page
20
DOI
10.1186/1750-9378-6-20

Leptospirosis among hospitalized febrile patients in northern Tanzania.

We enrolled consecutive febrile admissions to two hospitals in Moshi, Tanzania. Confirmed leptospirosis was defined as a ≥ 4-fold increase in microscopic agglutination test (MAT) titer; probable leptospirosis as reciprocal MAT titer ≥ 800; and exposure to pathogenic leptospires as titer ≥ 100. Among 870 patients enrolled in the study, 453 (52.1%) had paired sera available, and 40 (8.8%) of these met the definition for confirmed leptospirosis. Of 832 patients with ≥ 1 serum sample available, 30 (3.6%) had probable leptospirosis and an additional 277 (33.3%) had evidence of exposure to pathogenic leptospires. Among those with leptospirosis the most common clinical diagnoses were malaria in 31 (44.3%) and pneumonia in 18 (25.7%). Leptospirosis was associated with living in a rural area (odds ratio [OR] 3.4, P < 0.001). Among those with confirmed leptospirosis, the predominant reactive serogroups were Mini and Australis. Leptospirosis is a major yet underdiagnosed cause of febrile illness in northern Tanzania, where it appears to be endemic.

Authors
Biggs, HM; Bui, DM; Galloway, RL; Stoddard, RA; Shadomy, SV; Morrissey, AB; Bartlett, JA; Onyango, JJ; Maro, VP; Kinabo, GD; Saganda, W; Crump, JA
MLA Citation
Biggs, HM, Bui, DM, Galloway, RL, Stoddard, RA, Shadomy, SV, Morrissey, AB, Bartlett, JA, Onyango, JJ, Maro, VP, Kinabo, GD, Saganda, W, and Crump, JA. "Leptospirosis among hospitalized febrile patients in northern Tanzania." Am J Trop Med Hyg 85.2 (August 2011): 275-281.
Website
http://hdl.handle.net/10161/6334
PMID
21813847
Source
pubmed
Published In
American Journal of Tropical Medicine and Hygiene
Volume
85
Issue
2
Publish Date
2011
Start Page
275
End Page
281
DOI
10.4269/ajtmh.2011.11-0176

Q fever, spotted fever group, and typhus group rickettsioses among hospitalized febrile patients in northern Tanzania.

BACKGROUND: The importance of Q fever, spotted fever group rickettsiosis (SFGR), and typhus group rickettsiosis (TGR) as causes of febrile illness in sub-Saharan Africa is unknown; the putative role of Q fever as a human immunodeficiency virus (HIV) coinfection is unclear. METHODS: We identified febrile inpatients in Moshi, Tanzania, from September 2007 through August 2008 and collected acute- and convalescent-phase serum samples. A ≥4-fold increase in immunoglobulin (Ig) G immunfluorescence assay (IFA) titer to Coxiella burnetii phase II antigen defined acute Q fever. A ≥4-fold increase in IgG IFA titer to Rickettsia conorii or Rickettsia typhi antigen defined SFGR and TGR, respectively. RESULTS: Among 870 patients, 483 (55.5%) were tested for acute Q fever, and 450 (51.7%) were tested for acute SFGR and TGR. Results suggested acute Q fever in 24 (5.0%) patients and SFGR and TGR in 36 (8.0%) and 2 (0.5%) patients, respectively. Acute Q fever was associated with hepato- or splenomegaly (odds ratio [OR], 3.1; P = .028), anemia (OR, 3.0; P = .009), leukopenia (OR, 3.9; P = .013), jaundice (OR, 7.1; P = .007), and onset during the dry season (OR, 2.7; P = .021). HIV infection was not associated with acute Q fever (OR, 1.7; P = .231). Acute SFGR was associated with leukopenia (OR, 4.1; P = .003) and with evidence of other zoonoses (OR, 2.2; P = .045). CONCLUSIONS: Despite being common causes of febrile illness in northern Tanzania, Q fever and SFGR are not diagnosed or managed with targeted antimicrobials. C. burnetii does not appear to be an HIV-associated co-infection.

Authors
Prabhu, M; Nicholson, WL; Roche, AJ; Kersh, GJ; Fitzpatrick, KA; Oliver, LD; Massung, RF; Morrissey, AB; Bartlett, JA; Onyango, JJ; Maro, VP; Kinabo, GD; Saganda, W; Crump, JA
MLA Citation
Prabhu, M, Nicholson, WL, Roche, AJ, Kersh, GJ, Fitzpatrick, KA, Oliver, LD, Massung, RF, Morrissey, AB, Bartlett, JA, Onyango, JJ, Maro, VP, Kinabo, GD, Saganda, W, and Crump, JA. "Q fever, spotted fever group, and typhus group rickettsioses among hospitalized febrile patients in northern Tanzania." Clin Infect Dis 53.4 (August 2011): e8-15.
PMID
21810740
Source
pubmed
Published In
Clinical Infectious Diseases
Volume
53
Issue
4
Publish Date
2011
Start Page
e8
End Page
15
DOI
10.1093/cid/cir411

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania.

OBJECTIVE: To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. METHODS: During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV-1 RNA PCR was performed on those aged <18 months. HIV-infected patients also received serum cryptococcal antigen testing and had their CD4-positive T-lymphocyte count and percent determined. RESULTS: A total of 467 patients were enrolled whose median age was 2 years (range 2 months-13 years); Of those patients, 57.2% were female and 12.2% were HIV-infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV-uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. CONCLUSION: Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over-diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co-infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.

Authors
Crump, JA; Ramadhani, HO; Morrissey, AB; Msuya, LJ; Yang, L-Y; Chow, S-C; Morpeth, SC; Reyburn, H; Njau, BN; Shaw, AV; Diefenthal, HC; Bartlett, JA; Shao, JF; Schimana, W; Cunningham, CK; Kinabo, GD
MLA Citation
Crump, JA, Ramadhani, HO, Morrissey, AB, Msuya, LJ, Yang, L-Y, Chow, S-C, Morpeth, SC, Reyburn, H, Njau, BN, Shaw, AV, Diefenthal, HC, Bartlett, JA, Shao, JF, Schimana, W, Cunningham, CK, and Kinabo, GD. "Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania." Trop Med Int Health 16.7 (July 2011): 830-837.
PMID
21470347
Source
pubmed
Published In
Tropical Medicine & International Health
Volume
16
Issue
7
Publish Date
2011
Start Page
830
End Page
837
DOI
10.1111/j.1365-3156.2011.02774.x

A cost-effectiveness analysis of alternative HIV retesting strategies in sub-saharan Africa.

BACKGROUND: Guidelines in sub-Saharan Africa on when HIV-seronegative persons should retest range from never to annually for lower-risk populations and from annually to every 3 months for high-risk populations. METHODS: We designed a mathematical model to compare the cost-effectiveness of alternative HIV retesting frequencies. Cost of HIV counseling and testing, linkage to care, treatment costs, disease progression, and mortality, and HIV transmission are modeled for three hypothetical cohorts with posited annual HIV incidence of 0.8%, 1.3%, and 4.0%, respectively. The model compared costs, quality-adjusted life-years gained, and secondary infections averted from testing intervals ranging from 3 months to 30 years. Input parameters from sub-Saharan Africa were used and explored in sensitivity analyses. RESULTS: Accounting for secondary infections averted, the most cost-effective testing frequency was every 7.5 years for 0.8% incidence, every 5 years for 1.3% incidence, and every 2 years for 4.0% incidence. Optimal testing strategies and their relative cost-effectiveness were most sensitive to assumptions about HIV counseling and testing and treatment costs, rates of CD4 decline, rates of HIV transmission, and whether tertiary infections averted were taken into account. CONCLUSIONS: While higher risk populations merit more frequent HIV testing than low risk populations, regular retesting is beneficial even in low-risk populations. Our data demonstrate benefits of tailoring testing intervals to resource constraints and local HIV incidence rates.

Authors
Waters, RC; Ostermann, J; Reeves, TD; Masnick, MF; Thielman, NM; Bartlett, JA; Crump, JA
MLA Citation
Waters, RC, Ostermann, J, Reeves, TD, Masnick, MF, Thielman, NM, Bartlett, JA, and Crump, JA. "A cost-effectiveness analysis of alternative HIV retesting strategies in sub-saharan Africa." J Acquir Immune Defic Syndr 56.5 (April 15, 2011): 443-452.
PMID
21297484
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
56
Issue
5
Publish Date
2011
Start Page
443
End Page
452
DOI
10.1097/QAI.0b013e3182118f8c

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania.

BACKGROUND: few studies describe patterns of human immunodeficiency virus (HIV) co-infections in African hospitals in the antiretroviral therapy (ART) era. METHODS: we enrolled consecutive admitted patients aged ≥ 13 years with oral temperature of ≥ 38.0°C during 1 year in Moshi, Tanzania. A standardized clinical history and physical examination was done and hospital outcome recorded. HIV antibody testing, aerobic and mycobacterial blood cultures, and malaria film were performed. HIV-infected patients also received serum cryptococcal antigen testing and CD4(+) T lymphocyte count (CD4 cell count). RESULTS: of 403 patients enrolled, the median age was 38 years (range, 14-96 years), 217 (53.8%) were female, and 157 (39.0%) were HIV-infected. Of HIV-infected patients, the median CD4 cell count was 98 cells/μL (range, 1-1,105 cells/ μL), 20 (12.7%) were receiving ART, and 29 (18.5%) were receiving trimethoprim-sulfamethoxazole prophylaxis. There were 112 (27.7%) patients who had evidence of invasive disease, including 26 (23.2%) with Salmonella serotype Typhi infection, 24 (21.4%) with Streptococcus pneumoniae infection, 17 (15.2%) with Cryptococcus neoformans infection, 12 (10.7%) with Mycobacterium tuberculosis complex infection, 8 (7.1%) with Plasmodium falciparum infection, and 7 (6.3%) with Escherichia coli infection. HIV infection was associated with M. tuberculosis and C. neoformans bloodstream infection but not with E. coli, S. pneumoniae, or P. falciparum infection. HIV infection appeared to be protective against Salmonella. Typhi bloodstream infection (odds ratio, .12; P = .001). CONCLUSIONS: while Salmonella Typhi and S. pneumoniae were the most common causes of invasive infection overall, M. tuberculosis and C. neoformans were the leading causes of bloodstream infection among HIV-infected inpatients in Tanzania in the ART era. We demonstrate a protective effect of HIV against Salmonella. Typhi bloodstream infection in this setting. HIV co-infections continue to account for a large proportion of febrile admissions in Tanzania.

Authors
Crump, JA; Ramadhani, HO; Morrissey, AB; Saganda, W; Mwako, MS; Yang, L-Y; Chow, S-C; Morpeth, SC; Reyburn, H; Njau, BN; Shaw, AV; Diefenthal, HC; Shao, JF; Bartlett, JA; Maro, VP
MLA Citation
Crump, JA, Ramadhani, HO, Morrissey, AB, Saganda, W, Mwako, MS, Yang, L-Y, Chow, S-C, Morpeth, SC, Reyburn, H, Njau, BN, Shaw, AV, Diefenthal, HC, Shao, JF, Bartlett, JA, and Maro, VP. "Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania." Clin Infect Dis 52.3 (February 1, 2011): 341-348.
PMID
21217181
Source
pubmed
Published In
Clinical Infectious Diseases
Volume
52
Issue
3
Publish Date
2011
Start Page
341
End Page
348
DOI
10.1093/cid/ciq103

Who tests, who doesn't, and why? Uptake of mobile HIV counseling and testing in the Kilimanjaro Region of Tanzania.

BACKGROUND: Optimally, expanded HIV testing programs should reduce barriers to testing while attracting new and high-risk testers. We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing (MVCT) campaigns in four rural villages in the Kilimanjaro Region of Tanzania. METHODS: Between December 2007 and April 2008, 878 MVCT participants and 506 randomly selected community residents who did not access MVCT were surveyed. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing between MVCT participants and community residents who did not access MVCT. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing, between the two groups. RESULTS: MVCT clients reported greater HIV exposure risk (OR 1.20 [1.04 to 1.38] for males; OR 1.11 [1.03 to 1.19] for females). Female MVCT clients were more likely to report low household expenditures (OR 1.47 [1.04 to 2.05]), male clients reported higher rates of unstable income sources (OR 1.99 [1.22 to 3.24]). First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested (OR 2.17 [1.05 to 4.48] for males; OR 5.95 [2.85 to 12.45] for females). HIV-related stigma, fears of testing or test disclosure, and not being able to leave work were strongly associated with non-participation in MVCT (ORs from 0.11 to 0.84). CONCLUSIONS: MVCT attracted clients with increased exposure risk and fewer economic resources; HIV related stigma and testing-related fears remained barriers to testing. MVCT did not disproportionately attract either first-time or frequent repeat testers. Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk populations.

Authors
Ostermann, J; Reddy, EA; Shorter, MM; Muiruri, C; Mtalo, A; Itemba, DK; Njau, B; Bartlett, JA; Crump, JA; Thielman, NM
MLA Citation
Ostermann, J, Reddy, EA, Shorter, MM, Muiruri, C, Mtalo, A, Itemba, DK, Njau, B, Bartlett, JA, Crump, JA, and Thielman, NM. "Who tests, who doesn't, and why? Uptake of mobile HIV counseling and testing in the Kilimanjaro Region of Tanzania. (Published online)" PLoS One 6.1 (January 31, 2011): e16488-.
Website
http://hdl.handle.net/10161/5955
PMID
21304973
Source
pubmed
Published In
PloS one
Volume
6
Issue
1
Publish Date
2011
Start Page
e16488
DOI
10.1371/journal.pone.0016488

Establishment of haematological and immunological reference values for healthy Tanzanian children in Kilimanjaro Region.

OBJECTIVE: To determine the normal haematological and immunological reference intervals for healthy Tanzanian children. METHODS: We analysed data from 655 HIV-seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross-sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents. RESULTS: Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4-positive T-lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4-positive T-lymphocyte percentages are lower than established developed country medians. CONCLUSIONS: Country-specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4-positive T-lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.

Authors
Buchanan, AM; Muro, FJ; Gratz, J; Crump, JA; Musyoka, AM; Sichangi, MW; Morrissey, AB; M'rimberia, JK; Njau, BN; Msuya, LJ; Bartlett, JA; Cunningham, CK
MLA Citation
Buchanan, AM, Muro, FJ, Gratz, J, Crump, JA, Musyoka, AM, Sichangi, MW, Morrissey, AB, M'rimberia, JK, Njau, BN, Msuya, LJ, Bartlett, JA, and Cunningham, CK. "Establishment of haematological and immunological reference values for healthy Tanzanian children in Kilimanjaro Region." Trop Med Int Health 15.9 (September 2010): 1011-1021.
PMID
20636301
Source
pubmed
Published In
Tropical Medicine & International Health
Volume
15
Issue
9
Publish Date
2010
Start Page
1011
End Page
1021
DOI
10.1111/j.1365-3156.2010.02585.x

Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study.

BACKGROUND: Many HIV care and treatment programs in resource-limited settings rely on clinical and immunologic monitoring of antiretroviral therapy (ART), but accuracy of this strategy to detect virologic failure (VF) among children has not been evaluated. METHODS: A cross-sectional sample of HIV-infected children aged 1-16 years on ART >or=6 months receiving care at a Tanzanian referral center underwent clinical staging, CD4 lymphocyte measurement, plasma HIV-1 RNA level, and complete blood count. Associations with VF (HIV-1 RNA >or=400 copies/mL) were determined utilizing bivariable and multivariate analyses; accuracy of current clinical and immunologic guidelines in identifying children with VF was assessed. FINDINGS: Of 206 children (median age 8.7 years, ART duration 2.4 years), 65 (31.6%) demonstrated VF at enrollment. Clinical and immunological criteria identified 2 (3.5%) of 57 children with VF on first-line therapy, exhibiting 3.5% sensitivity and 100% specificity. VF was associated with younger age, receipt of nevirapine vs. efavirenz-based regimen, CD4% < 25%, and physician documentation of maladherence (P < 0.05 on bivariable analysis); the latter 2 factors remained significant on multivariate logistic regression. INTERPRETATION: This study demonstrates poor performance of clinical and immunologic criteria in identifying children with virologic failure. Affordable techniques for measuring HIV-1 RNA level applicable in resource-limited settings are urgently needed.

Authors
Emmett, SD; Cunningham, CK; Mmbaga, BT; Kinabo, GD; Schimana, W; Swai, ME; Bartlett, JA; Crump, JA; Reddy, EA
MLA Citation
Emmett, SD, Cunningham, CK, Mmbaga, BT, Kinabo, GD, Schimana, W, Swai, ME, Bartlett, JA, Crump, JA, and Reddy, EA. "Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study." J Acquir Immune Defic Syndr 54.4 (August 2010): 368-375.
PMID
20216225
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
54
Issue
4
Publish Date
2010
Start Page
368
End Page
375
DOI
10.1097/QAI.0b013e3181cf4882

Microalbuminuria predicts overt proteinuria among patients with HIV infection.

BACKGROUND: This study examines the association between microalbuminuria and the development of proteinuria among HIV-infected persons. METHODS: A total of 948 subjects provided urine samples for albumin, protein and creatinine measurements semiannually. Microalbuminuria was defined as an albumin-to-creatinine ratio of >30 mg/g. Proteinuria was defined as a protein-to-creatinine ratio of > or =0.350 mg/mg. The progression from microalbuminuria to proteinuria was described. RESULTS: At baseline, 69.4% of the subjects had no detectable proteinuria, 20.2% had microalbuminuria, and 10.4% had proteinuria. Subjects with microalbuminuria and proteinuria were more likely to be black (P=0.02), have lower CD4 cell counts (P=0.02 comparing subjects without abnormal urine protein excretion to subjects with microalbuminuria; P=0.0001 comparing subjects with microalbuminuria to subjects with proteinuria), and have a higher HIV RNA level (P=0.08 and 0.04, respectively). Among 658 subjects with normal urine protein, 82.7% continued to have no abnormality, 14.3% developed microalbuminuria, and 3.0% developed proteinuria. Subjects without baseline proteinuria (i.e. either normal protein excretion or microalbuminuria) who developed proteinuria were more likely to have microalbuminuria (P=0.001), a lower CD4 cell count (P=0.06), and a higher plasma HIV RNA (P=0.03) than those who did not progress to proteinuria. In multivariate analysis, only microalbuminuria remained associated with the development of proteinuria (odds ratio 2.9; 95% confidence interval 1.5, 5.5; P=0.001). CONCLUSION: Microalbuminuria predicts the development of proteinuria among HIV-infected persons. Because proteinuria has been linked to poorer outcomes, strategies to affect microalbuminuria should be tested.

Authors
Szczech, LA; Menezes, P; Byrd Quinlivan, E; van der Horst, C; Bartlett, JA; Svetkey, LP
MLA Citation
Szczech, LA, Menezes, P, Byrd Quinlivan, E, van der Horst, C, Bartlett, JA, and Svetkey, LP. "Microalbuminuria predicts overt proteinuria among patients with HIV infection." HIV Med 11.7 (August 2010): 419-426.
PMID
20059571
Source
pubmed
Published In
HIV Medicine
Volume
11
Issue
7
Publish Date
2010
Start Page
419
End Page
426
DOI
10.1111/j.1468-1293.2009.00805.x

Reply to 'Quantification of HIV-1 RNA on Dried Blood Spots' AIDS 24:475-6

Authors
Lofgren, SM; Stevens, WS; Bartlett, JA; Crump, JA
MLA Citation
Lofgren, SM, Stevens, WS, Bartlett, JA, and Crump, JA. "Reply to 'Quantification of HIV-1 RNA on Dried Blood Spots' AIDS 24:475-6." AIDS 24.5 (2010): 785-786.
PMID
20215884
Source
scival
Published In
AIDS
Volume
24
Issue
5
Publish Date
2010
Start Page
785
End Page
786
DOI
10.1097/QAD.0b013e32833653c5

Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania.

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.

Authors
Shao, HJ; Crump, JA; Ramadhani, HO; Uiso, LO; Ole-Nguyaine, S; Moon, AM; Kiwera, RA; Woods, CW; Shao, JF; Bartlett, JA; Thielman, NM
MLA Citation
Shao, HJ, Crump, JA, Ramadhani, HO, Uiso, LO, Ole-Nguyaine, S, Moon, AM, Kiwera, RA, Woods, CW, Shao, JF, Bartlett, JA, and Thielman, NM. "Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania." AIDS Res Hum Retroviruses 25.12 (December 2009): 1277-1285.
Website
http://hdl.handle.net/10161/5969
PMID
20001518
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
25
Issue
12
Publish Date
2009
Start Page
1277
End Page
1285
DOI
10.1089/aid.2009.0100

Characteristics of HIV voluntary counseling and testing clients before and during care and treatment scale-up in Moshi, Tanzania.

OBJECTIVES: We evaluated changes in characteristics of clients presenting for voluntary counseling and testing (VCT) before and during care and treatment center (CTC) scale-up activities in Moshi, Tanzania, between November 2003 and December 2007. METHODS: Consecutive clients were surveyed after pretest counseling, and rapid HIV antibody testing was performed. Trend tests were used to assess changes in seroprevalence and client characteristics over time. Multivariable logistic regression models were used to estimate the contribution of changes in sociodemographic and behavioral risk characteristics, and symptoms, to changes in seroprevalence before and during CTC scale-up. RESULTS: Data from 4391 first-time VCT clients were analyzed. HIV seroprevalence decreased from 26.2% to 18.9% after the availability of free antiretroviral therapy and expansion of CTCs beyond regional and referral hospitals. Seroprevalence decreased by 27 % for females (P = 0.0002) and 34% for males (P = 0.0125). Declines in seropositivity coincided with decreases in symptoms among males and females (P < 0.0001) and a more favorable distribution of sociodemographic risks among females (P = 0.002). No changes in behavioral risk characteristics were observed. CONCLUSIONS: Concurrent with the scale-up of CTCs, HIV seroprevalence and rates of symptoms declined sharply at an established freestanding VCT site in Moshi, Tanzania. If more HIV-infected persons access VCT at sites where antiretrovirals are offered, freestanding VCT sites may become a less cost-effective means for HIV case finding.

Authors
Shorter, MM; Ostermann, J; Crump, JA; Tribble, AC; Itemba, DK; Mgonja, A; Mtalo, A; Bartlett, JA; Shao, JF; Schimana, W; Thielman, NM
MLA Citation
Shorter, MM, Ostermann, J, Crump, JA, Tribble, AC, Itemba, DK, Mgonja, A, Mtalo, A, Bartlett, JA, Shao, JF, Schimana, W, and Thielman, NM. "Characteristics of HIV voluntary counseling and testing clients before and during care and treatment scale-up in Moshi, Tanzania." J Acquir Immune Defic Syndr 52.5 (December 2009): 648-654.
PMID
19675465
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
52
Issue
5
Publish Date
2009
Start Page
648
End Page
654
DOI
10.1097/QAI.0b013e3181b31a6a

Evaluation of a dried blood spot HIV-1 RNA program for early infant diagnosis and viral load monitoring at rural and remote healthcare facilities.

OBJECTIVE: To assess technical and operational performance of a dried blood spot (DBS)-based HIV-1 RNA service for remote healthcare facilities in a low-income country. DESIGN: A method comparison and operational evaluation of DBS RNA against conventional tests for early infant diagnosis of HIV and HIV RNA quantitation under field conditions in Tanzania. METHODS: DBSs were prepared and plasma was frozen at -80 degrees C. DBSs were mailed and plasma couriered to a central laboratory for testing using the Abbott m2000 system. Infant diagnosis DBSs were also tested for HIV-1 DNA by ROCHE COBAS AmpliPrep/COBAS TaqMan System. Results of DBS RNA were compared with conventional tests; program performance was described. RESULTS: Among 176 infant diagnosis participants, using a threshold of at least 1000 copies/ml, sensitivity and specificity of DBS versus plasma RNA were 1.00 and 0.99, and of DBS RNA versus DBS DNA were 0.97 and 1.00. Among 137 viral load monitoring participants, when plasma and DBS RNA were compared, r value was 0.9709; r value was 0.9675 for at least 5000 copies/ml but was 0.7301 for less than 5000 copies/ml. The highest plasma RNA value at which DBS RNA was not detected was 2084 copies/ml. Median (range) turnaround time from sample collection to result receipt at sites was 23 (4-69) days. The Tanzania mail service successfully transmitted all DBS and results between sites and the central laboratory. CONCLUSION: Under program conditions in Tanzania, DBS provided HIV-1 RNA results comparable to conventional methods to remote healthcare facilities. DBS RNA testing is an alternative to liquid plasma for HIV-1 RNA services in remote areas.

Authors
Lofgren, SM; Morrissey, AB; Chevallier, CC; Malabeja, AI; Edmonds, S; Amos, B; Sifuna, DJ; von Seidlein, L; Schimana, W; Stevens, WS; Bartlett, JA; Crump, JA
MLA Citation
Lofgren, SM, Morrissey, AB, Chevallier, CC, Malabeja, AI, Edmonds, S, Amos, B, Sifuna, DJ, von Seidlein, L, Schimana, W, Stevens, WS, Bartlett, JA, and Crump, JA. "Evaluation of a dried blood spot HIV-1 RNA program for early infant diagnosis and viral load monitoring at rural and remote healthcare facilities." AIDS 23.18 (November 27, 2009): 2459-2466.
PMID
19741481
Source
pubmed
Published In
AIDS
Volume
23
Issue
18
Publish Date
2009
Start Page
2459
End Page
2466
DOI
10.1097/QAD.0b013e328331f702

Missed opportunities for diagnosis of tuberculosis and human immunodeficiency virus co-infection in Moshi, Tanzania.

SETTING: A community-based voluntary counseling and testing (VCT) center in Moshi, Tanzania. OBJECTIVE: To compare rates of prior human immunodeficiency virus (HIV) testing among clients with and without previous tuberculosis (TB) treatment, and HIV seropositivity among those with and without current TB symptoms. DESIGN: Cross-sectional study of consecutive clients presenting for initial testing; sociodemographic and clinical data were collected via a structured questionnaire. HIV status was compared among clients with or without three or more TB-related symptoms: weight loss, fever, cough, hemoptysis or night sweats. RESULTS: Overall, 225 (3%) of 6583 VCT clients who responded to questions on previous TB treatment reported a history of TB, but only 34 (15%) reported previous HIV testing. This rate of HIV testing was not different from the rate among those clients without a history of TB (OR 0.77, P = 0.175). One hundred thirty-five (61%) clients with a history of TB were HIV-infected at VCT, compared with 17% of all clients. Of the total 6592 first-time testers who responded, 372 (6%) had at least three symptoms suggestive of TB at VCT. These symptoms were strongly associated with HIV seropositivity (OR 16.30, P < 0.001). CONCLUSION: Missed opportunities for HIV diagnosis at the time of TB treatment appear frequent in this population, underscoring the need for integration of TB and HIV diagnostic services.

Authors
Tribble, AC; Hamilton, CD; Crump, JA; Mgonja, A; Mtalo, A; Ndanu, E; Itemba, DK; Landman, KZ; Shorter, M; Ndosi, EM; Shao, JF; Bartlett, JA; Thielman, NM
MLA Citation
Tribble, AC, Hamilton, CD, Crump, JA, Mgonja, A, Mtalo, A, Ndanu, E, Itemba, DK, Landman, KZ, Shorter, M, Ndosi, EM, Shao, JF, Bartlett, JA, and Thielman, NM. "Missed opportunities for diagnosis of tuberculosis and human immunodeficiency virus co-infection in Moshi, Tanzania." Int J Tuberc Lung Dis 13.10 (October 2009): 1260-1266.
PMID
19793431
Source
pubmed
Published In
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Volume
13
Issue
10
Publish Date
2009
Start Page
1260
End Page
1266

Successes, challenges, and limitations of current antiretroviral therapy in low-income and middle-income countries.

As a result of the scale-up of antiretroviral treatment (ART) programmes and substantial financial support worldwide, an increasing number of HIV-infected individuals in low-income and middle-income countries (LIMCs) now have access to ART. Despite this progress, important questions remain on the best use of ART and how patients should be maintained on a successful regimen. This Review addresses some of the issues faced by those managing the epidemic in LMICs, including when to start treatment, choice of first-line ART, and when to switch regimens. Although the first priority must be continued expansion of access to ART, there should be a move towards starting ART earlier to treat individuals before they reach advanced stages of disease, to reduce early mortality, and to build support for improved monitoring of treatment failure. There is also a need for more randomised controlled studies to identify the long-term outcomes, cost-effectiveness of ART, and use of virological monitoring in LMICs.

Authors
Bartlett, JA; Shao, JF
MLA Citation
Bartlett, JA, and Shao, JF. "Successes, challenges, and limitations of current antiretroviral therapy in low-income and middle-income countries." Lancet Infect Dis 9.10 (October 2009): 637-649. (Review)
PMID
19778766
Source
pubmed
Published In
Lancet Infectious Diseases
Volume
9
Issue
10
Publish Date
2009
Start Page
637
End Page
649
DOI
10.1016/S1473-3099(09)70227-0

Obstacles and proposed solutions to effective antiretroviral therapy in resource-limited settings.

More than 3 million people were receiving antiretroviral therapy (ART) at the end of 2007, but this number represents only 31% of people clinically eligible for ART in resource-limited settings. The primary objective of this study is to summarize the key obstacles that impede the goal of universal access prevention, care, and treatment. We performed a systematic literature search to review studies that reported barriers to diagnosis and access to treatment of HIV/AIDS in resource-limited countries. Persons living with HIV/ AIDS commonly face economic, sociocultural, and behavioral obstacles to access treatment and care for HIV. A variety of programs to overcome these barriers have been implemented, including efforts to destigmatize HIV/AIDS, enhance treatment literacy, provide income-generation skills, decentralize HIV services, promote gender equality, and adopt a multisectoral approach to optimize limited resources. An understanding of these obstacles and suggested methods to overcome them must be addressed by global policy makers before universal ART access can be achieved.

Authors
Bartlett, JA; Hornberger, J; Shewade, A; Bhor, M; Rajagopalan, R
MLA Citation
Bartlett, JA, Hornberger, J, Shewade, A, Bhor, M, and Rajagopalan, R. "Obstacles and proposed solutions to effective antiretroviral therapy in resource-limited settings." J Int Assoc Physicians AIDS Care (Chic) 8.4 (July 2009): 253-268. (Review)
PMID
19721103
Source
pubmed
Published In
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002)
Volume
8
Issue
4
Publish Date
2009
Start Page
253
End Page
268
DOI
10.1177/1545109709337745

Morbidity and mortality among a cohort of HIV-infected adults in a programme for community home-based care, in the Kilimanjaro Region of Tanzania (2003-2005).

Community home-based care (CHBC) plays an integral role in the care of HIV-infected patients living in resource-limited regions. A longitudinal cohort study has recently been conducted, in the Kilimanjaro Region of northern Tanzania, in order to identify the components of an effective CHBC programme. Structured questionnaires were administered to clients over two census rounds, one in October 2003-February 2004 and the other in January 2005-October 2005. In the second round, follow-up interviews were completed for 226 (87.9%) of the 257 clients included in the first round. The clients included in the first round had a median (range) age of 38 (20-66) years and 182 (75.2%) of them were female. Although only 27 (12.9%) of them were using antiretroviral therapy (ART) when first interviewed, 108 (44.6%) were taking trimethoprim-sulfamethoxazole (SXT) prophylaxis. By the time of the follow-up interviews, 102 (45.1%) of the clients included in the first round had died, giving a mortality of 51/100 person-years of observation. The primary cause of death for 87 (85.3%) of the clients who had died was respiratory and/or gastro-intestinal infection, and the most common contributory causes of death were malnutrition (81.4%) and anaemia (42.2%). On bivariable analysis, the following first-round conditions were found to be significantly associated with death by the second census round: weakness for >1 month [odds ratio (OR)=2.64; P=0.008]; oral thrush (OR=2.31; P=0.015); painful swallowing (OR=2.02; P=0.036); staying in bed for part of the day over most of the previous month (OR=1.94; P=0.017); fever for >1 month (OR=1.95; P=0.016); and severe bacterial infections (OR=1.80; P=0.036). The high mortality was associated with advanced, symptomatic HIV disease for which antiretroviral therapy was indicated. Clients who were in the advanced stages of HIV disease (as defined by the World Health Organization's criteria) in the first census round were significantly more likely to have died by the time of the second round than the other clients investigated (log-rank chi(2)=8.115; P=0.044). The high level of morbidity observed in this study, and the causes of mortality that were identified, emphasise the need for CHBC programmes to provide HIV-infected patients with improved access to basic resources such as SXT and isoniazid prophylaxis, clean water, oral rehydration therapy, and micronutrient supplementation, in addition to increased access to ART.

Authors
Tillekeratne, LG; Thielman, NM; Kiwera, RA; Chu, HY; Kaale, L; Morpeth, SC; Ostermann, J; Mtweve, SP; Shao, JF; Bartlett, JA; Crump, JA
MLA Citation
Tillekeratne, LG, Thielman, NM, Kiwera, RA, Chu, HY, Kaale, L, Morpeth, SC, Ostermann, J, Mtweve, SP, Shao, JF, Bartlett, JA, and Crump, JA. "Morbidity and mortality among a cohort of HIV-infected adults in a programme for community home-based care, in the Kilimanjaro Region of Tanzania (2003-2005)." Ann Trop Med Parasitol 103.3 (April 2009): 263-273.
PMID
19341540
Source
pubmed
Published In
Annals of Tropical Medicine & Parasitology
Volume
103
Issue
3
Publish Date
2009
Start Page
263
End Page
273
DOI
10.1179/136485909X398203

Invasive disease caused by nontuberculous mycobacteria, Tanzania.

Data on nontuberculous mycobacterial (NTM) disease in sub-Saharan Africa are limited. During 2006-2008, we identified 3 HIV-infected patients in northern Tanzania who had invasive NTM; 2 were infected with "Mycobacterium sherrisii" and 1 with M. avium complex sequevar MAC-D. Invasive NTM disease is present in HIV-infected patients in sub-Saharan Africa.

Authors
Crump, JA; van Ingen, J; Morrissey, AB; Boeree, MJ; Mavura, DR; Swai, B; Thielman, NM; Bartlett, JA; Grossman, H; Maro, VP; van Soolingen, D
MLA Citation
Crump, JA, van Ingen, J, Morrissey, AB, Boeree, MJ, Mavura, DR, Swai, B, Thielman, NM, Bartlett, JA, Grossman, H, Maro, VP, and van Soolingen, D. "Invasive disease caused by nontuberculous mycobacteria, Tanzania." Emerg Infect Dis 15.1 (January 2009): 53-55.
PMID
19116050
Source
pubmed
Published In
Emerging infectious diseases
Volume
15
Issue
1
Publish Date
2009
Start Page
53
End Page
55
DOI
10.3201/eid1501.081093

Stavudine in first-line antiretroviral regimens in resource-limited settings: Time for a better solution

Authors
Bartlett, JA; Maro, VP
MLA Citation
Bartlett, JA, and Maro, VP. "Stavudine in first-line antiretroviral regimens in resource-limited settings: Time for a better solution." HIV Therapy 3.2 (2009): 109-111.
Source
scival
Published In
HIV Therapy
Volume
3
Issue
2
Publish Date
2009
Start Page
109
End Page
111
DOI
10.2217/17584310.3.2.109

Delaying a treatment switch in antiretroviral-treated HIV type 1-infected patients with detectable drug-resistant viremia does not have a profound effect on immune parameters: AIDS Clinical Trials Group Study A5115

Some patients are unable to achieve and maintain an undetectable plasma HIV-1 RNA level with combination antiretroviral therapy (ART) and are therefore maintained on a partially suppressive regimen. To determine the immune consequences of continuing ART despite persistent viremia, we randomized 47 ART-treated individuals with low to moderate plasma HIV-1 RNA levels (200-9999 copies/ml) to either an immediate switch in therapy or a delayed switch (when plasma HIV-1 RNA became ≥10,000 copies/ml). After 48 weeks of follow-up, naive and memory CD4+ T cell percents were comparable in the two groups. The proportion of subjects with a lymphocyte proliferative response to Candida, Mycobacterium avium- intracellulare complex, or HIV-gag was also not significantly different at week 48. Delaying a treatment switch in patients with partial virologic suppression and stable CD4+ T cells does not have profound effects on immune parameters. © Copyright 2009, Mary Ann Liebert, Inc.

Authors
Tenorio, AR; Jiang, H; Zheng, Y; Bastow, B; Kuritzkes, DR; Bartlett, JA; Deeks, SG; Landay, AL; Riddler, SA
MLA Citation
Tenorio, AR, Jiang, H, Zheng, Y, Bastow, B, Kuritzkes, DR, Bartlett, JA, Deeks, SG, Landay, AL, and Riddler, SA. "Delaying a treatment switch in antiretroviral-treated HIV type 1-infected patients with detectable drug-resistant viremia does not have a profound effect on immune parameters: AIDS Clinical Trials Group Study A5115." AIDS Research and Human Retroviruses 25.2 (2009): 135-139.
PMID
19239354
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
25
Issue
2
Publish Date
2009
Start Page
135
End Page
139
DOI
10.1089/aid.2008.0200

Low sensitivity of T-cell based detection of tuberculosis among HIV co-infected Tanzanian in-patients.

OBJECTIVE: To evaluate the performance of QuantiFERON-TB GOLD (QFTG) in a resource-poor setting among patients with and without HIV infection. DESIGN: Cross-sectional study. SETTING: Two hospitals in Northern Tanzania. SUBJECTS: Eighty three adult male and female inpatients. INTERVENTION: All patients were screened for HIV infection and underwent tuberculin skin test (TST) and QFTG. RESULTS: Eighty-three subjects were enrolled, and 29 (35%) of 83 were HIV-infected. QFTG yielded indeterminate results in 12 (22%; 95% CI 12%-34%) of 54 HIV-uninfected and 13 (45%; 95% CI 26%-64%) of 29 HIV-infected subjects (p = 0.0323). Among those with smear-positive pulmonary tuberculosis, TST was positive in 40 (100%; 95% CI 91%-100%) of 40 HIV-uninfected subjects compared with seven (54%; 95% CI 25%-81%) of 13 HIV-infected subjects (p < 0.0001), and QFTG was positive in 28 (70%; 95% CI 53%-83%) of 40 HIV-uninfected subjects compared with three (23%; 95% CI 5%-54%) of 13 HIV-infected subjects (p = 0.0029). Among medical inpatients at risk for latent tuberculosis infection, TST was positive in seven (50%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p = 0.0701) and QFTG was positive among two (14%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p = 0.7437). CONCLUSIONS: The presence of HIV co-infection was associated with a significant reduction in sensitivity of both the TST (p < 0.0001) and QFTG (p = 0.0029) for the diagnosis of active M. tuberculosis infection. The high proportion of indeterminate QFTG and lack of sensitivity, particularly among HIV-infected patients, may limit its applicability in settings like Tanzania. Larger studies in resource-poor settings are required.

Authors
Seshadri, C; Uiso, LO; Ostermann, J; Diefenthal, H; Shao, HJ; Chu, HY; Asmuth, DM; Thielman, NM; Bartlett, JA; Crump, JA
MLA Citation
Seshadri, C, Uiso, LO, Ostermann, J, Diefenthal, H, Shao, HJ, Chu, HY, Asmuth, DM, Thielman, NM, Bartlett, JA, and Crump, JA. "Low sensitivity of T-cell based detection of tuberculosis among HIV co-infected Tanzanian in-patients." East Afr Med J 85.9 (September 2008): 442-449.
PMID
19537417
Source
pubmed
Published In
East African medical journal
Volume
85
Issue
9
Publish Date
2008
Start Page
442
End Page
449

Gender differences in the risk of HIV infection among persons reporting abstinence, monogamy, and multiple sexual partners in northern Tanzania.

BACKGROUND: Monogamy, together with abstinence, partner reduction, and condom use, is widely advocated as a key behavioral strategy to prevent HIV infection in sub-Saharan Africa. We examined the association between the number of sexual partners and the risk of HIV seropositivity among men and women presenting for HIV voluntary counseling and testing (VCT) in northern Tanzania. METHODOLOGY/ PRINCIPAL FINDINGS: Clients presenting for HIV VCT at a community-based AIDS service organization in Moshi, Tanzania were surveyed between November 2003 and December 2007. Data on sociodemographic characteristics, reasons for testing, sexual behaviors, and symptoms were collected. Men and women were categorized by number of lifetime sexual partners, and rates of seropositivity were reported by category. Factors associated with HIV seropositivity among monogamous males and females were identified by a multivariate logistic regression model. Of 6,549 clients, 3,607 (55%) were female, and the median age was 30 years (IQR 24-40). 939 (25%) females and 293 (10%) males (p<0.0001) were HIV seropositive. Among 1,244 (34%) monogamous females and 423 (14%) monogamous males, the risk of HIV infection was 19% and 4%, respectively (p<0.0001). The risk increased monotonically with additional partners up to 45% (p<0.001) and 15% (p<0.001) for women and men, respectively with 5 or more partners. In multivariate analysis, HIV seropositivity among monogamous women was most strongly associated with age (p<0.0001), lower education (p<0.004), and reporting a partner with other partners (p = 0.015). Only age was a significant risk factor for monogamous men (p = 0.0004). INTERPRETATION: Among women presenting for VCT, the number of partners is strongly associated with rates of seropositivity; however, even women reporting lifetime monogamy have a high risk for HIV infection. Partner reduction should be coupled with efforts to place tools in the hands of sexually active women to reduce their risk of contracting HIV.

Authors
Landman, KZ; Ostermann, J; Crump, JA; Mgonja, A; Mayhood, MK; Itemba, DK; Tribble, AC; Ndosi, EM; Chu, HY; Shao, JF; Bartlett, JA; Thielman, NM
MLA Citation
Landman, KZ, Ostermann, J, Crump, JA, Mgonja, A, Mayhood, MK, Itemba, DK, Tribble, AC, Ndosi, EM, Chu, HY, Shao, JF, Bartlett, JA, and Thielman, NM. "Gender differences in the risk of HIV infection among persons reporting abstinence, monogamy, and multiple sexual partners in northern Tanzania. (Published online)" PLoS One 3.8 (August 27, 2008): e3075-.
Website
http://hdl.handle.net/10161/4504
PMID
18728779
Source
pubmed
Published In
PloS one
Volume
3
Issue
8
Publish Date
2008
Start Page
e3075
DOI
10.1371/journal.pone.0003075

Effect of trimethoprim-sulfamethoxazole prophylaxis on antimicrobial resistance of fecal Escherichia coli in HIV-infected patients in Tanzania.

BACKGROUND: Trimethoprim-sulfamethoxazole (SXT) reduces morbidity and mortality among HIV-infected persons in Africa, but its impact on antimicrobial resistance is of concern. METHODS: HIV-uninfected (group A), HIV-infected but not requiring SXT (group B), and HIV-infected and eligible for SXT (group C) adults were recruited into a prospective observational cohort study in Moshi, Tanzania. Stool was examined for Escherichia coli nonsusceptible to SXT at baseline and at weeks 1, 2, 4, and 24. General estimating equation models were used to assess differences in susceptibility over time and cross-resistance to other antimicrobials. RESULTS: Of 181 subjects, 118 (65.1%) were female and the median (range) age was 36 (20 to 72) years. At baseline, E. coli nonsusceptible to SXT was isolated from 23 (53.5%) of 43 patients in group A, 25 (67.6%) of 37 patients in group B, and 37 (64.9%) of 57 patients in group C. The odds ratios (P value) for SXT nonsusceptibility in group C at weeks 1, 2, 4, and 24 compared with baseline were 3.4 (0.013), 3.0 (0.019), 2.9 (0.030), and 1.5 (0.515), respectively. SXT nonsusceptibility was associated with nonsusceptibility to ampicillin, chloramphenicol, ciprofloxacin, and nalidixic acid (P

Authors
Morpeth, SC; Thielman, NM; Ramadhani, HO; Hamilton, JD; Ostermann, J; Kisenge, PR; Shao, HJ; Reller, LB; Itemba, DK; Sam, NE; Bartlett, JA; Shao, JF; Crump, JA
MLA Citation
Morpeth, SC, Thielman, NM, Ramadhani, HO, Hamilton, JD, Ostermann, J, Kisenge, PR, Shao, HJ, Reller, LB, Itemba, DK, Sam, NE, Bartlett, JA, Shao, JF, and Crump, JA. "Effect of trimethoprim-sulfamethoxazole prophylaxis on antimicrobial resistance of fecal Escherichia coli in HIV-infected patients in Tanzania." J Acquir Immune Defic Syndr 47.5 (April 15, 2008): 585-591.
PMID
18285712
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
47
Issue
5
Publish Date
2008
Start Page
585
End Page
591
DOI
10.1097/QAI.0b013e31816856db

Predictors of incomplete adherence, virologic failure, and antiviral drug resistance among HIV-infected adults receiving antiretroviral therapy in Tanzania.

BACKGROUND: Access to antiretroviral therapy is rapidly expanding in sub-Saharan Africa. Identifying the predictors of incomplete adherence, virologic failure, and antiviral drug resistance is essential to achieving long-term success. METHODS: A total of 150 subjects who had received antiretroviral therapy for at least 6 months completed a structured questionnaire and adherence assessment, and plasma human immunodeficiency virus (HIV) RNA levels were measured. Virologic failure was defined as an HIV RNA level >400 copies/mL; for patients with an HIV RNA level >1000 copies/mL, genotypic antiviral drug resistance testing was performed. Predictors were analyzed using bivariable and multivariable logistic regression models. RESULTS: A total of 23 (16%) of 150 subjects reported incomplete adherence. Sacrificing health care for other necessities (adjusted odds ratio [AOR], 19.8; P<.01) and the proportion of months receiving self-funded treatment (AOR, 23.5; P=.04) were associated with incomplete adherence. Virologic failure was identified in 48 (32%) of 150 subjects and was associated with incomplete adherence (AOR, 3.6; P=.03) and the proportion of months receiving self-funded antiretroviral therapy (AOR, 13.0; P=.02). Disclosure of HIV infection status to family members or others was protective against virologic failure (AOR, 0.10; P=.04). CONCLUSIONS: Self-funded treatment was associated with incomplete adherence and virologic failure, and disclosure of HIV infection status was protective against virologic failure. Efforts to provide free antiretroviral therapy and to promote social coping may enhance adherence and reduce rates of virologic failure.

Authors
Ramadhani, HO; Thielman, NM; Landman, KZ; Ndosi, EM; Gao, F; Kirchherr, JL; Shah, R; Shao, HJ; Morpeth, SC; McNeill, JD; Shao, JF; Bartlett, JA; Crump, JA
MLA Citation
Ramadhani, HO, Thielman, NM, Landman, KZ, Ndosi, EM, Gao, F, Kirchherr, JL, Shah, R, Shao, HJ, Morpeth, SC, McNeill, JD, Shao, JF, Bartlett, JA, and Crump, JA. "Predictors of incomplete adherence, virologic failure, and antiviral drug resistance among HIV-infected adults receiving antiretroviral therapy in Tanzania." Clin Infect Dis 45.11 (December 1, 2007): 1492-1498.
PMID
17990233
Source
pubmed
Published In
Clinical Infectious Diseases
Volume
45
Issue
11
Publish Date
2007
Start Page
1492
End Page
1498
DOI
10.1086/522991

Predicting CD4 lymphocyte count <200 cells/mm(3) in an HIV type 1-infected African population.

Clinical criteria are recommended to select HIV-infected patients for initiation of antiretroviral therapy when CD4 lymphocyte testing is unavailable. We evaluated the performance characteristics of WHO staging criteria, anthropometrics, and simple laboratory measurements for predicting CD4 lymphocyte count (CD4 count) <200 cells/mm(3) among HIV-infected patients in Tanzania. A total of 202 adults, diagnosed with HIV infection through community-based testing, underwent a detailed evaluation including staging history and examination, anthropometry, complete blood count, erythrocyte sedimentation rate (ESR), and CD4 count. Univariable analysis and recursive partitioning were used to identify characteristics associated with CD4 count 200 cells/mm(3). Of 202 participants 109 (54%) had a CD4 count <200 cells/mm(3). Characteristics most strongly associated with CD4 count <200 cells/mm(3) (p-value <0.0001) were the presence of mucocutaneous manifestations (72% vs. 28%), lower total lymphocyte count (TLC) (median 1,450 vs. 2,200 cells/mm(3)), lower total white blood cell count (median 4,200 vs. 5,500 cells/mm(3)), and higher ESR (median 95 vs. 53 mm/h). In a partition tree model, TLC <1,200 cells/mm(3), ESR >or=120 mm/h, or the presence of mucocutaneous manifestations yielded a sensitivity of 0.85 and specificity of 0.63 for predicting CD4 count <200 cells/mm(3). The sensitivity of the 2006 WHO Staging system improved from 0.75 to 0.93 with inclusion of these parameters, at the expense of specificity (0.36 to 0.26). The presence of mucocutaneous manifestations, TLC <1,200 cells/mm(3), or ESR >or=120 mm/h was a strong predictor of CD4 count <200 cells/mm(3) and enhanced the sensitivity of the 2006 WHO staging criteria for identifying patients likely to benefit from antiretrovirals.

Authors
Morpeth, SC; Crump, JA; Shao, HJ; Ramadhani, HO; Kisenge, PR; Moylan, CA; Naggie, S; Caram, LB; Landman, KZ; Sam, NE; Itemba, DK; Shao, JF; Bartlett, JA; Thielman, NM
MLA Citation
Morpeth, SC, Crump, JA, Shao, HJ, Ramadhani, HO, Kisenge, PR, Moylan, CA, Naggie, S, Caram, LB, Landman, KZ, Sam, NE, Itemba, DK, Shao, JF, Bartlett, JA, and Thielman, NM. "Predicting CD4 lymphocyte count <200 cells/mm(3) in an HIV type 1-infected African population." AIDS Res Hum Retroviruses 23.10 (October 2007): 1230-1236.
PMID
17961109
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
23
Issue
10
Publish Date
2007
Start Page
1230
End Page
1236
DOI
10.1089/aid.2007.0053

Comparative efficacy of nucleoside/nucleotide reverse transcriptase inhibitors in combination with efavirenz: results of a systematic overview.

BACKGROUND: Many trials of antiretroviral therapy in treatment-naïve subjects have investigated the relative efficacy of the third drug in a treatment regimen. However, the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) components may also affect efficacy. METHOD: A systematic overview of clinical trials studying initial treatment in naïve subjects receiving efavirenz-containing regimens and providing week 48 time to loss of virologic response (TLOVR) results was undertaken to compare results with different NRTI combinations. RESULTS: Seven trials studying 3,807 subjects were identified that met the inclusion criteria. Baseline characteristics were similar across studies. Using the week 48 TLOVR results as the primary method of comparison, combinations of tenofovir and lamivudine or emtricitabine appeared to provide improved virologic responses. Similar results were obtained when the proportions of subjects with plasma HIV RNA levels <50 copies/mL were examined.

Authors
Bartlett, JA; Chen, S-S; Quinn, JB
MLA Citation
Bartlett, JA, Chen, S-S, and Quinn, JB. "Comparative efficacy of nucleoside/nucleotide reverse transcriptase inhibitors in combination with efavirenz: results of a systematic overview." HIV Clin Trials 8.4 (July 2007): 221-226. (Review)
PMID
17720662
Source
pubmed
Published In
HIV clinical trials
Volume
8
Issue
4
Publish Date
2007
Start Page
221
End Page
226
DOI
10.1310/hct0804-221

Antiretroviral treatment literacy among HIV voluntary counseling and testing clients in Moshi, Tanzania, 2003 to 2005.

Antiretroviral treatment literacy leads to greater HIV testing and treatment and antiretroviral treatment adherence. Among northern Tanzanian subjects, antiretroviral treatment awareness was only 17%. Factors associated with low antiretroviral treatment literacy included having exchanged money or gifts for sex, living in rural areas, having more than 2 children, and having a primary education only. Previous HIV testing was protective against low antiretroviral treatment literacy. These results support refocusing HIV education efforts and increasing synergy between HIV prevention and treatment programs.

Authors
Landman, KZ; Thielman, NM; Mgonja, A; Shao, HJ; Itemba, DK; Ndosi, EM; Tribble, AC; Shao, JF; Bartlett, JA; Crump, JA
MLA Citation
Landman, KZ, Thielman, NM, Mgonja, A, Shao, HJ, Itemba, DK, Ndosi, EM, Tribble, AC, Shao, JF, Bartlett, JA, and Crump, JA. "Antiretroviral treatment literacy among HIV voluntary counseling and testing clients in Moshi, Tanzania, 2003 to 2005." J Int Assoc Physicians AIDS Care (Chic) 6.1 (March 2007): 24-26.
PMID
17329501
Source
pubmed
Published In
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002)
Volume
6
Issue
1
Publish Date
2007
Start Page
24
End Page
26
DOI
10.1177/1545109706298479

Generic and branded drugs for the treatment of people living with HIV/AIDS.

HIV/AIDS care has benefited tremendously from the availability of antiretroviral (ARV) drugs, both branded and generic. Drug discovery and innovation is the result of direct investment in the development of branded medications, a crucial process for future improvements in care. However, the cost of branded medications is too high for resource-limited countries, where most persons with HIV/AIDS live. Generic drugs dramatically lower the cost of care; however, their safety and efficacy must be ensured and maintained. Proven bioavailability and bioequivalence, in addition to satisfactory manufacturing, distribution, and administration, are keys to successfully implementing the use of qualified generic ARVs. Agencies such as the US Food and Drug Administration (FDA), European Medicines Agency (EMEA), and the World Health Organization (WHO), continue to strengthen the surveillance process through which qualified generic and branded drugs are provided worldwide. Generic drugs have the potential to cause harm if rigorous standards for their use are not followed, but those that are qualified offer great promise in the treatment of HIV/AIDS.

Authors
Bartlett, JA; Muro, EP
MLA Citation
Bartlett, JA, and Muro, EP. "Generic and branded drugs for the treatment of people living with HIV/AIDS." J Int Assoc Physicians AIDS Care (Chic) 6.1 (March 2007): 15-23. (Review)
PMID
17329500
Source
pubmed
Published In
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002)
Volume
6
Issue
1
Publish Date
2007
Start Page
15
End Page
23
DOI
10.1177/1545109707299856

Detection of minor drug-resistant populations by parallel allele-specific sequencing.

We developed a highly sensitive parallel allele-specific sequencing (PASS) assay to simultaneously analyze a large number of viral genomes and detect minor drug-resistant populations at approximately 0.1-0.01% levels. Using this assay on samples from individuals infected with human immunodeficiency viruses (HIV), we successfully detected and quantified minor populations of drug-resistant viruses and performed linkage analysis of multiple-drug resistance mutations. This assay may serve as a useful tool to study drug resistance in HIV and other infectious agents.

Authors
Cai, F; Chen, H; Hicks, CB; Bartlett, JA; Zhu, J; Gao, F
MLA Citation
Cai, F, Chen, H, Hicks, CB, Bartlett, JA, Zhu, J, and Gao, F. "Detection of minor drug-resistant populations by parallel allele-specific sequencing." Nat Methods 4.2 (February 2007): 123-125.
PMID
17206150
Source
pubmed
Published In
Nature Methods
Volume
4
Issue
2
Publish Date
2007
Start Page
123
End Page
125
DOI
10.1038/nmeth995

Decreasing CD4+ T-cell count during suppressed or low-level viraemia in patients with HIV infection.

BACKGROUND: Suboptimal improvement in CD4+ T-cell count is not uncommon in HIV-infected patients with suppressed plasma HIV RNA levels, and a decrease in CD4+ T-cell count in patients with suppressed or low-level viraemia has been observed. METHODS: Our objectives were to identify the prevalence of decreasing CD4+ T-cell counts during suppressed or low-level viraemia, to determine the frequency of clinical events during and immediately after such decreases, and to examine for associations with individual variables. A matched case-control study was undertaken using the Duke Infectious Diseases Clinic database (n = 3,949). Cases had at least two consecutive significant decreases in either CD4+ absolute count or CD4+ percentage, while also having plasma HIV RNA levels < 1,000 copies/ml. RESULTS: The prevalence of decreasing CD4+ T-cell counts during suppressed or low-level viraemia was 1.22%. Only three HIV-associated clinical events occurred. The majority of cases had an increase in the CD4+ T-cell count immediately following the study period. The use of either zidovudine or stavudine was weakly associated with decreasing CD4+ T-cell counts in a multivariable analysis, but this association was not present in cases with only a decrease in CD4+ T-cell percentage. CONCLUSIONS: Decreasing CD4+ T-cell counts during suppressed or low-level viraemia are rare, typically transient, and not associated with an increase in HIV-associated clinical events.

Authors
Anderson, AML; Kosinski, AS; Bartlett, JA
MLA Citation
Anderson, AML, Kosinski, AS, and Bartlett, JA. "Decreasing CD4+ T-cell count during suppressed or low-level viraemia in patients with HIV infection." Antivir Ther 12.7 (2007): 1041-1048.
PMID
18018762
Source
pubmed
Published In
Antiviral therapy
Volume
12
Issue
7
Publish Date
2007
Start Page
1041
End Page
1048

A randomized study of antiviral medication switch at lower- versus higher-switch thresholds: AIDS clinical trials group study A5115

Background: Clinical stability has been observed with continued antiretroviral therapy (ART) in the setting of partial virological suppression. The optimal time to switch treatment in patients with low but detectable HIV-1 RNA is not known. Methods: Subjects on stable ART with HIV-1 RNA 200-10,000 copies/ml were randomized to an immediate treatment switch, or to a delayed switch when HIV-1 RNA increased to ≥10,000 copies/ml or CD4+ T-cell count decreased by 20%. The primary outcome measures were immune activation (proportion of CD8+ T-cells expressing CD38 at week 48) and evolution of genotypic drug resistance. Results: The study failed to fully accrue the originally planned 108 subjects. Only 47 subjects were randomized to immediate- or delayed-switch arms. Of the subjects in the delayed-switch arm, 10/23 (43%) met the criteria for ART switch during the study (median follow-up 82 weeks). After 48 weeks of observation, the level of immune activation was comparable in the two arms. New resistance mutations were observed in 3/17 and 8/19 subjects in the immediate- and delayed-switch groups, respectively. The loss of future treatment options, however, was comparable in the delayed- and immediate-switch groups. Conclusions: Individuals with partial viral suppression tend to remain immunologically stable, however, the accumulation of drug resistance mutations is an ongoing risk. Delayed switch in ART may be a reasonable short-term strategy for individuals with very limited treatment options. © 2007 International Medical Press.

Authors
Riddler, SA; Jiang, H; Tenorio, A; Huang, H; Kuritzkes, DR; Acosta, EP; Landay, A; Bastow, B; Haas, DW; Tashima, KT; Jain, MK; Deeks, SG; Bartlett, JA
MLA Citation
Riddler, SA, Jiang, H, Tenorio, A, Huang, H, Kuritzkes, DR, Acosta, EP, Landay, A, Bastow, B, Haas, DW, Tashima, KT, Jain, MK, Deeks, SG, and Bartlett, JA. "A randomized study of antiviral medication switch at lower- versus higher-switch thresholds: AIDS clinical trials group study A5115." Antiviral Therapy 12.4 (2007): 531-541.
PMID
17668562
Source
scival
Published In
Antiviral therapy
Volume
12
Issue
4
Publish Date
2007
Start Page
531
End Page
541

Erratum: ProteomeBinders: Planning a European resource of affinity reagents for analysis of the human proteome (Nature Methods (2007) vol. 4 (13-17))

Authors
Cai, F; Chen, H; Hicks, CB; Bartlett, JA; Zhu, J; Gao, F
MLA Citation
Cai, F, Chen, H, Hicks, CB, Bartlett, JA, Zhu, J, and Gao, F. "Erratum: ProteomeBinders: Planning a European resource of affinity reagents for analysis of the human proteome (Nature Methods (2007) vol. 4 (13-17))." Nature Methods 4.2 (2007): 187--.
Source
scival
Published In
Nature Methods
Volume
4
Issue
2
Publish Date
2007
Start Page
187-
DOI
10.1038/nmeth0207-187a

Long-term results of initial therapy with abacavir and Lamivudine combined with Efavirenz, Amprenavir/Ritonavir, or Stavudine.

OBJECTIVE: To compare alternative class-sparing antiretroviral regimens in treatment-naive subjects. DESIGN: Open-label, multicenter, randomized trial of up to 3 consecutive treatment regimens over 96 weeks. METHODS: Two hundred ninety-one subjects received abacavir (ABC) and lamivudine and efavirenz (nonnucleoside reverse transcriptase inhibitors [NNRTIs]), ritonavir-boosted amprenavir (protease inhibitor [PI]), or stavudine (nucleoside reverse transcriptase inhibitor [NRTI]) by random assignment. The primary end points were the percentages of subjects with plasma HIV-1 RNA levels <400 copies/mL and time to treatment failure over 96 weeks. RESULTS: Ninety percent of subjects completed 96 weeks of follow-up, and 79% remained on study treatment. At week 96, there were no differences between arms in the percentages of subjects with plasma HIV-1 RNA levels <400 and <50 copies/mL, mean changes in plasma HIV-1 RNA levels, time to treatment failure, time to first or second virologic failure, or CD4 cell counts. The NNRTI arm had a greater percentages of subjects with RNA levels

Authors
Bartlett, JA; Johnson, J; Herrera, G; Sosa, N; Rodriguez, A; Liao, Q; Griffith, S; Irlbeck, D; Shaefer, MS; Clinically Significant Long-Term Antiretroviral Sequential Sequencing Study (CLASS) Team,
MLA Citation
Bartlett, JA, Johnson, J, Herrera, G, Sosa, N, Rodriguez, A, Liao, Q, Griffith, S, Irlbeck, D, Shaefer, MS, and Clinically Significant Long-Term Antiretroviral Sequential Sequencing Study (CLASS) Team, . "Long-term results of initial therapy with abacavir and Lamivudine combined with Efavirenz, Amprenavir/Ritonavir, or Stavudine." J Acquir Immune Defic Syndr 43.3 (November 1, 2006): 284-292.
PMID
16967040
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
43
Issue
3
Publish Date
2006
Start Page
284
End Page
292
DOI
10.1097/01.qai.0000243092.40490.26

An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults.

OBJECTIVE: To compare the effectiveness of three drug combination antiretroviral therapy (ART) in treatment-naive HIV-infected persons, and identify the predictors of responses. DESIGN AND METHODS: Overview of trials identified by searching public domain publications and conference presentations. The three-drug combination therapy was defined as two nucleoside reverse transcriptase inhibitors (NRTI) or nucleotide and NRTI, and either: (1) a protease inhibitor (PI); (2) a non-nucleoside RTI (NNRTI); (3) a third NRTI; or (4) a ritonavir-boosted PI (BPI). Week 24 and 48 results for the proportions of patients with plasma HIV RNA levels < 400 and < 50 copies/ml, and change in CD4(+) cell counts were recorded. RESULTS: Fifty-three trials met the entry criteria, and enrolled 14 264 patients into 90 treatment arms. Overall 55% of patients had plasma HIV RNA levels < 50 copies/ml at week 48 and this percentage increased with later publication dates. In unadjusted pairwise comparisons at week 48, significantly greater percentages of patients receiving NNRTI (64%) and BPI (64%) had RNA < 50 copies/ml than NRTI (54%) or PI (43%), and CD4(+) cell count increases were significantly greater in the BPI group (+200 cells/microl) than the PI (+179), NNRTI (+173), or NRTI (+161) groups. Pill count and percentage of patients with week 48 plasma HIV RNA levels < 50 copies/ml were correlated in the univariate analysis (P = 0.0053; r = -0.323), but pill count was not a significant predictor in the multivariate analyses. Drug class and baseline CD4(+) cell counts were significant predictors, but explained only a modest amount of the treatment effect, (R(2) = 0.355). CONCLUSIONS: NNRTI and BPI-containing regimens offer superior virologic suppression over 48 weeks, supporting existing guidelines for the choice of initial ART. Pill count was not a consistent predictor of virologic suppression.

Authors
Bartlett, JA; Fath, MJ; Demasi, R; Hermes, A; Quinn, J; Mondou, E; Rousseau, F
MLA Citation
Bartlett, JA, Fath, MJ, Demasi, R, Hermes, A, Quinn, J, Mondou, E, and Rousseau, F. "An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults." AIDS 20.16 (October 24, 2006): 2051-2064. (Review)
PMID
17053351
Source
pubmed
Published In
AIDS
Volume
20
Issue
16
Publish Date
2006
Start Page
2051
End Page
2064
DOI
10.1097/01.aids.0000247578.08449.ff

Changing antiretroviral therapy in the setting of virologic relapse: review of the current literature.

Virologic relapse after initial virologic suppression remains a concern for patients on antiretroviral therapy (ART). Multiple factors may contribute to virologic relapse, including suboptimal adherence, resistance, and pharmacokinetic issues. The major guidelines for HIV care are in agreement that ART regimen change is indicated in relapse because resistance is identified, but the guidelines are not completely clear on the timing of regimen change. When relapse occurs due to resistance, patients may continue with viremia well below their set points, stable or increasing CD4+ counts, and clinical health for several years. However, delaying a switch in the treatment regimen may lead to the accumulation of resistance which compromises future treatment response. In general, a lower switch threshold is recommended for patients during relapse on first or second line regimens.

Authors
Anderson, AML; Bartlett, JA
MLA Citation
Anderson, AML, and Bartlett, JA. "Changing antiretroviral therapy in the setting of virologic relapse: review of the current literature." Curr HIV/AIDS Rep 3.2 (July 2006): 79-85. (Review)
PMID
16608664
Source
pubmed
Published In
Current HIV/AIDS Reports
Volume
3
Issue
2
Publish Date
2006
Start Page
79
End Page
85

Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview.

OBJECTIVE: To identify optimal first-line therapies based on the rate of virologic success (VS) and the preservation of future treatment options in antiretroviral therapy (ART)-naive subjects. DESIGN: Systematic overview of genotypic resistance mutations from clinical trials of combination ART. METHODS: Various sources were searched for studies in ART-naive subjects providing virologic response rates and genotypes from subjects with virologic failure. The International AIDS Society-USA genotypic resistance guidelines were used to calculate regimen resistance cost (RCreg) and number of active drug (AD) scores for each regimen and to rank the regimens. RESULTS: Intra- and interstudy comparisons showed higher VS rates for nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens (range: 51%-76%) and boosted protease inhibitor (boosted PI) regimens (range: 55%-79%). Boosted PI failures had the lowest RCreg (range: 0.12-0.21) and the highest AD (range: 19.80-20.18) scores. NNRTI failures had higher RCreg (range: 0.00-1.22) and lower AD (range: 16.83-21) scores. CONCLUSIONS: NNRTI and boosted PI regimens provide the highest rates of VS in treatment-naive HIV-infected persons. Treatment option scores were higher in subjects who failed boosted PI- containing regimens versus NNRTI-containing regimens, however.

Authors
Bartlett, JA; Buda, JJ; von Scheele, B; Mauskopf, JA; Davis, EA; Elston, R; King, MS; Lanier, ER
MLA Citation
Bartlett, JA, Buda, JJ, von Scheele, B, Mauskopf, JA, Davis, EA, Elston, R, King, MS, and Lanier, ER. "Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview." J Acquir Immune Defic Syndr 41.3 (March 2006): 323-331. (Review)
PMID
16540933
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
41
Issue
3
Publish Date
2006
Start Page
323
End Page
331
DOI
10.1097/01.qai.0000197070.69859.f3

Cost-effectiveness of free HIV voluntary counseling and testing through a community-based AIDS service organization in Northern Tanzania.

OBJECTIVES: We evaluated the cost-effectiveness of fee-based and free testing strategies at an HIV voluntary counseling and testing (VCT) program integrated into a community-based AIDS service organization in Moshi, Tanzania. METHODS: We waived the usual fee schedule during a 2-week free, advertised VCT campaign; analyzed the number of clients testing per day during prefree, free, and postfree testing periods; and estimated the cost-effectiveness of limited and sustained free testing strategies. RESULTS: The number of clients testing per day increased from 4.1 during the prefree testing interval to 15.0 during the free testing campaign (P<.0001) and remained significantly increased at 7.1 (P<.0001) after resumption of the standard fees. HIV seroprevalence (16.7%) and risk behaviors were unchanged over these intervals. Modeled over 1 year, the costs per infection averted with the standard fee schedule, with a 2-week free VCT campaign, and with sustained free VCT year-round were $170, $105, and $92, respectively, and the costs per disability-adjusted life year gained were $8.72, $5.40, and $4.72, respectively. CONCLUSIONS: The provision of free VCT enhances both the number of clients testing per day and its cost-effectiveness in resource-limited settings.

Authors
Thielman, NM; Chu, HY; Ostermann, J; Itemba, DK; Mgonja, A; Mtweve, S; Bartlett, JA; Shao, JF; Crump, JA
MLA Citation
Thielman, NM, Chu, HY, Ostermann, J, Itemba, DK, Mgonja, A, Mtweve, S, Bartlett, JA, Shao, JF, and Crump, JA. "Cost-effectiveness of free HIV voluntary counseling and testing through a community-based AIDS service organization in Northern Tanzania." Am J Public Health 96.1 (January 2006): 114-119.
PMID
16317205
Source
pubmed
Published In
American journal of public health
Volume
96
Issue
1
Publish Date
2006
Start Page
114
End Page
119
DOI
10.2105/AJPH.2004.056796

Pharmacogenetics of nevirapine-associated hepatotoxicity: An adult AIDS Clinical Trials Group Collaboration

Associations have been reported between an MDR1 variant and responses to nonnucleoside reverse-transcriptase inhibitors. We explored associations between MDR1, CYP2B6, and CYP3A polymorphisms and nevirapine hepatotoxicity. Among participants in a randomized study in South Africa (FTC-302), MDR1 3435C→T was significantly associated with decreased risk of hepatotoxicity (risk ratio, 0.30; P = .016). © 2006 by the Infectious Diseases Society of America. All rights reserved.

Authors
Haas, DW; Bartlett, JA; Andersen, JW; Sanne, I; Wilkinson, GR; Hinkle, J; Rousseau, F; Ingram, CD; Shaw, A; Lederman, MM; Kim, RB
MLA Citation
Haas, DW, Bartlett, JA, Andersen, JW, Sanne, I, Wilkinson, GR, Hinkle, J, Rousseau, F, Ingram, CD, Shaw, A, Lederman, MM, and Kim, RB. "Pharmacogenetics of nevirapine-associated hepatotoxicity: An adult AIDS Clinical Trials Group Collaboration." Clinical Infectious Diseases 43.6 (2006): 783-786.
PMID
16912957
Source
scival
Published In
Clinical Infectious Diseases
Volume
43
Issue
6
Publish Date
2006
Start Page
783
End Page
786
DOI
10.1086/507097

A prospective clinical and pathological examination of injection site reactions with the HIV-1 fusion inhibitor enfuvirtide.

OBJECTIVE: Antiretroviral regimens containing the fusion inhibitor enfuvirtide (ENF) are associated with sustained viral suppression and immunological benefit. However, local injection site reactions (ISR) occur in the majority of patients. The aim of this study was to determine the pathogenesis of ISRs. METHODS: Injection sites were evaluated prospectively from 30 min up to 15-30 days post-injection in ENF-experienced (Cohort I) and ENF-naive patients (Cohort II) during the first 2 weeks of therapy. Four to five injections were given in rotating abdominal sites by a nurse using a standardized technique and were rigorously evaluated. RESULTS: Reactions were observed in 80-100% of patients; the majority of the reactions were mild to moderate, generally appeared within 24-48 h post-injection, and pain, induration and erythema were the most common clinical signs. Whereas most patients experienced ISRs, the overall prevalence in Cohort II was low (35% maximum). Punch biopsies of injection sites in Cohort I consisted primarily of mixed lymphocytic infiltrates with eosinophils and neutrophils. Injection vehicle (ENF buffer minus ENF) and reduced volume (2 x 0.5 ml ENF [45 mg] versus 1.0 ml [90 mg] ENF) were investigated in Cohort II. Fewer reactions appeared with vehicle and pain was absent with the smaller injection volume. Pathology was indistinguishable between ENF, vehicle and normal tissue in Cohort II patients. CONCLUSION: These results suggest that injection technique, injection volume and peptide may influence ISR to ENF.

Authors
Myers, SA; Selim, AA; McDaniel, MA; Hall, R; Zhang, Y; Bartlett, JA; True, AL
MLA Citation
Myers, SA, Selim, AA, McDaniel, MA, Hall, R, Zhang, Y, Bartlett, JA, and True, AL. "A prospective clinical and pathological examination of injection site reactions with the HIV-1 fusion inhibitor enfuvirtide." Antivir Ther 11.7 (2006): 935-939.
PMID
17302257
Source
pubmed
Published In
Antiviral therapy
Volume
11
Issue
7
Publish Date
2006
Start Page
935
End Page
939

Fixed dose combination abacavir/lamivudine in the treatment of HIV-1 infection.

The fixed dose combination of abacavir with lamivudine represents a new treatment option for patients infected with HIV. Fixed dose combination abacavir/lamivudine has the convenience of one pill and once-daily dosing. It achieves comparable suppression of plasma HIV RNA with the pill's individual components dosed twice daily and with thymidine analogs combined with lamivudine. The combination is well tolerated, with the potential advantages of less lipoatrophy and fewer metabolic perturbations. However, the abacavir component may cause hypersensitivity reactions, which are reported in up to 8% of patients, and are potentially life threatening. Fixed dose combination abacavir/lamivudine should be considered as a viable treatment option for HIV-infected patients, particularly for those who have otherwise limited nucleoside reverse transcriptase inhibitor choices.

Authors
Anderson, AML; Bartlett, JA
MLA Citation
Anderson, AML, and Bartlett, JA. "Fixed dose combination abacavir/lamivudine in the treatment of HIV-1 infection." Expert Rev Anti Infect Ther 3.6 (December 2005): 871-883. (Review)
PMID
16307500
Source
pubmed
Published In
Expert Review of Anti-Infective Therapy
Volume
3
Issue
6
Publish Date
2005
Start Page
871
End Page
883
DOI
10.1586/14787210.3.6.871

Sociodemographic and clinical characteristics of clients presenting for HIV voluntary counselling and testing in Moshi, Tanzania.

HIV voluntary counselling and testing (VCT) reduces high-risk sexual behaviour. Factors associated with HIV infection in VCT clients have not been well characterized in northern Tanzania. We prospectively surveyed 813 VCT clients in Moshi, Tanzania. Clients were administered a questionnaire on sociodemographic characteristics, sexual behaviour, and health status. Blood was taken for rapid HIV antibody testing. Factors associated with HIV seropositivity were identified using multivariate logistic regression analysis. Of 813 clients, the seroprevalence was 16.7%. The strongest associations with seropositivity were reporting diarrhoea (odds ratio [OR] 10.4, 95% confidence interval [CI] 3.6-29.9), an ill sexual partner (OR 6.3, 95% CI 3.0-12.9), or being a woman (OR 3.5, 95% CI 2.0-6.3). In a separate regression, the number of symptoms also predicted HIV infection (OR 2.1, 95% CI 1.6-2.6). VCT clients who tested positive had more HIV-related symptoms suggesting presentation at a later stage of HIV infection.

Authors
Chu, HY; Crump, JA; Ostermann, J; Oenga, RB; Itemba, DK; Mgonja, A; Mtweve, S; Bartlett, JA; Shao, JF; Thielman, NM
MLA Citation
Chu, HY, Crump, JA, Ostermann, J, Oenga, RB, Itemba, DK, Mgonja, A, Mtweve, S, Bartlett, JA, Shao, JF, and Thielman, NM. "Sociodemographic and clinical characteristics of clients presenting for HIV voluntary counselling and testing in Moshi, Tanzania." Int J STD AIDS 16.10 (October 2005): 691-696.
PMID
16212718
Source
pubmed
Published In
International Journal of STD & AIDS
Volume
16
Issue
10
Publish Date
2005
Start Page
691
End Page
696

Naïve T cells are maintained in the periphery during the first 3 months of acute HIV-1 infection: implications for analysis of thymus function.

A key determinant of T cell dynamics in HIV-1 infection is the status of thymic function. To date, most studies of the impact of HIV-1 on the thymus during early HIV-1 infection have been done in samples collected in the interval of 3-12 months after infection. In this study, we have probed the status of thymic function and peripheral naive T cells in patients with acute HIV-1 infection diagnosed 18-72 days after the onset of symptoms. We found that peripheral CD4 and CD8 T cell proliferation was initially elevated, then waned over time. The fall in T cell proliferation correlated with a reduction in HIV-1 viral RNA levels and a rise in peripheral blood CD4+ CD25+ T cells. In spite of elevated T cell proliferation early on in primary HIV-1 infection, levels of naive phenotype CD4 and CD8 T cells and T cell receptor excision circle positive cells (sjTREC(+)) remained constant. Taken together with the observation that T cell proliferation normally dilutes peripheral T cell episomal sjTREC levels, these data suggested that thymopoiesis contributes to maintenance of the naive T cell pool during the earliest stages of HIV-1 infection (18-72 days).

Authors
Sempowski, GD; Hicks, CB; Eron, JJ; Bartlett, JA; Hale, LP; Ferrari, G; Edwards, LJ; Fiscus, S; Haynes, BF
MLA Citation
Sempowski, GD, Hicks, CB, Eron, JJ, Bartlett, JA, Hale, LP, Ferrari, G, Edwards, LJ, Fiscus, S, and Haynes, BF. "Naïve T cells are maintained in the periphery during the first 3 months of acute HIV-1 infection: implications for analysis of thymus function." J Clin Immunol 25.5 (September 2005): 462-472.
PMID
16160915
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
25
Issue
5
Publish Date
2005
Start Page
462
End Page
472
DOI
10.1007/s10875-005-5635-4

Antiretroviral rounds. A communication conundrum.

Authors
Henry, K; Bartlett, JA; Kojic, E; Flanigan, TP
MLA Citation
Henry, K, Bartlett, JA, Kojic, E, and Flanigan, TP. "Antiretroviral rounds. A communication conundrum." AIDS clinical care. 17.12 (2005): 115-116.
PMID
16388541
Source
scival
Published In
AIDS clinical care
Volume
17
Issue
12
Publish Date
2005
Start Page
115
End Page
116

Appropriate use of nevirapine for long-term therapy [1] (multiple letters)

Authors
Leith, J; Piliero, P; Storfer, S; Mayers, D; Hinzmann, R; Sanne, I; Rousseau, F; Bartlett, JA; Lederman, MM
MLA Citation
Leith, J, Piliero, P, Storfer, S, Mayers, D, Hinzmann, R, Sanne, I, Rousseau, F, Bartlett, JA, and Lederman, MM. "Appropriate use of nevirapine for long-term therapy [1] (multiple letters)." Journal of Infectious Diseases 192.3 (2005): 545-547.
PMID
15995971
Source
scival
Published In
Journal of Infectious Diseases
Volume
192
Issue
3
Publish Date
2005
Start Page
545
End Page
547
DOI
10.1086/431606

Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects

Human immunodeficiency virus (HIV)-infected South African patients (n = 468) received blinded lamivudine or emtricitabine, stavudine, and either nevirapine or efavirenz (based on screening viral load). Baseline characteristics were analyzed in univariate and multivariate regression, to identify risk factors for hepatotoxicity (grade 3 or greater increase in serum aminotransferase levels). The occurrence of early hepatotoxicity was 17% in the nevirapine group and 0% in the efavirenz group and was balanced between the lamivudine and emtricitabine arms. Two subjects died of hepatic failure. Independent risk factors were body-mass index (BMI) <18.5, female sex, serum albumin level <35 g/L, mean corpuscular volume >85 fL, plasma HIV-1 RNA load <20,000 copies/mL, aspartate aminotransferase level <75 IU/L, and lactate dehydrogenase level <164 IU/L. The use of nevirapine in female patients with a low BMI should be discouraged. © 2005 by the Infectious Diseases Society of America. All rights reserved.

Authors
Sanne, I; Mommeja-Marin, H; Hinkle, J; Bartlett, JA; Lederman, MM; Maartens, G; Wakeford, C; Shaw, A; Quinn, J; Gish, RG; Rousseau, F
MLA Citation
Sanne, I, Mommeja-Marin, H, Hinkle, J, Bartlett, JA, Lederman, MM, Maartens, G, Wakeford, C, Shaw, A, Quinn, J, Gish, RG, and Rousseau, F. "Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects." Journal of Infectious Diseases 191.6 (2005): 825-829.
PMID
15717255
Source
scival
Published In
Journal of Infectious Diseases
Volume
191
Issue
6
Publish Date
2005
Start Page
825
End Page
829
DOI
10.1086/428093

Definition of proteinuria among women with HIV infection.

Authors
Szczech, LA; Gange, SJ; van der Horst, C; Bartlett, JA; Young, M; Cohen, MH; Anastos, K; Klassen, PS; Svetkey, LP
MLA Citation
Szczech, LA, Gange, SJ, van der Horst, C, Bartlett, JA, Young, M, Cohen, MH, Anastos, K, Klassen, PS, and Svetkey, LP. "Definition of proteinuria among women with HIV infection." Kidney Int 65.4 (April 2004): 1519-. (Letter)
PMID
15086498
Source
pubmed
Published In
Kidney international
Volume
65
Issue
4
Publish Date
2004
Start Page
1519
DOI
10.1111/j.1523-1755.2004.555_2.x

Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV.

T-1249 is a 39-aa synthetic peptide that inhibits fusion of human immunodeficiency virus (HIV) to the host target cell. A 14-day open-label, phase 1/2 dose-escalation monotherapy study of the safety and antiretroviral activity of T-1249 was performed on 115 HIV-1-infected adults. At baseline, the majority of the patients had advanced HIV disease (baseline median CD4(+) cell count, 57 cells/microL) and had extensive pretreatment (i.e., pre-T-1249) experience with antiretroviral medications (median, 11 antiretroviral drugs). Patients received T-1249 monotherapy by subcutaneous injection, for 14 days, at doses ranging from 6.25 to 192 mg/day. T-1249 was generally well tolerated, and no dose-limiting toxicity was identified. Injection-site reactions were the most commonly reported adverse event (57%). Dose-dependent decreases in plasma HIV-1 RNA load were observed; the median maximum change from baseline across dose groups ranged from -0.29 log(10) copies/mL (95% confidence interval [CI], -0.43 to -0.05 log(10) copies/mL) for the lowest dose to -1.96 log(10) copies/mL (95% CI, -2.02 to -1.37 copies/mL) for the highest dose. These results indicate that T-1249 is a potent new therapeutic agent for HIV-1 infection.

Authors
Eron, JJ; Gulick, RM; Bartlett, JA; Merigan, T; Arduino, R; Kilby, JM; Yangco, B; Diers, A; Drobnes, C; DeMasi, R; Greenberg, M; Melby, T; Raskino, C; Rusnak, P; Zhang, Y; Spence, R; Miralles, GD
MLA Citation
Eron, JJ, Gulick, RM, Bartlett, JA, Merigan, T, Arduino, R, Kilby, JM, Yangco, B, Diers, A, Drobnes, C, DeMasi, R, Greenberg, M, Melby, T, Raskino, C, Rusnak, P, Zhang, Y, Spence, R, and Miralles, GD. "Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV." J Infect Dis 189.6 (March 15, 2004): 1075-1083.
PMID
14999611
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
189
Issue
6
Publish Date
2004
Start Page
1075
End Page
1083
DOI
10.1086/381707

HIV-associated morbidity, mortality and diagnostic testing opportunities among inpatients at a referral hospital in northern Tanzania.

Hospitalized patients with HIV infection are among the most likely to benefit from the expanding availability of anti-retroviral therapy in sub-Saharan Africa. Between 1990 and 2000, 3667 people known to be HIV-infected were admitted to Kilimanjaro Christian Medical Centre (KCMC) in Moshi, northen Tanzania. The level of inpatient mortality among these patients varied from 15%-21%, and the proportion of the HIV-infected patients admitted who were female increased significantly, from 45% at the start of the study period to 52% at the end (P <0.001). When the medical records for 1683 of the HIV-infected patients who had been admitted between 1996 and 2001 were reviewed, the most prevalent diagnoses on admission were found to be pulmonary tuberculosis (21%), malaria (14%) and gastro-enteritis/diarrhoea (12%) among the adults, and non-tubercular pulmonary infection (21%), pulmonary tuberculosis (19%) and gastro-enteritis/diarrhoea (12%) among the children. The crude odds ratios (OR) for inpatient death were greatest for adults presenting with meningitis [OR=3.7; 95% confidence interval (CI)=2.1-6.7], septicaemia (OR=2.9; CI=1.2-7.3) or renal disease (OR=2.6; CI=1.2-5.7), and mortality was higher for men than for women (OR=1.4; CI=1.1-1.8). A single-day, point-prevalence survey in September 2001, among the KCMC's inpatients, identified HIV infection in 21% of those surveyed, many (44%) of the patients found positive being previously unaware of their infection. HIV infection remains a major cause of hospitalization and mortality in Moshi. A policy of routine testing would increase the number of HIV infections detected, allowing improvements in case management and in the prevention of infection.

Authors
Ole-Nguyaine, S; Crump, JA; Kibiki, GS; Kiang, K; Taylor, J; Schimana, W; Bartlett, JA; Shao, JF; Hamilton, JD; Thielman, NM
MLA Citation
Ole-Nguyaine, S, Crump, JA, Kibiki, GS, Kiang, K, Taylor, J, Schimana, W, Bartlett, JA, Shao, JF, Hamilton, JD, and Thielman, NM. "HIV-associated morbidity, mortality and diagnostic testing opportunities among inpatients at a referral hospital in northern Tanzania." Ann Trop Med Parasitol 98.2 (March 2004): 171-179.
PMID
15035727
Source
pubmed
Published In
Annals of Tropical Medicine & Parasitology
Volume
98
Issue
2
Publish Date
2004
Start Page
171
End Page
179
DOI
10.1179/000349804225003163

Persistent antiretroviral activity of nucleoside analogues after prolonged zidovudine and lamivudine therapy as demonstrated by rapid loss of activity after discontinuation

Antiretroviral (ARV) treatment decisions are difficult for HIV-1-infected patients on complex treatment regimens who have partial suppression of HIV-1 replication and limited treatment options. Information on the ARV activity of the components of a complex regimen would be useful. Sixteen subjects who had received prolonged therapy with zidovudine (ZDV) and lamivudine (3TC), with a median duration of 32.5 months, were discontinuing this dual-nucleoside regimen and volunteered to have plasma HIV-1 RNA levels monitored over the 2 weeks after discontinuation. All subjects experienced an increase in HIV-1 RNA after discontinuation, with a median increase of 0.54 log10 copies/mL over 2 weeks (range: 0.31-1.71; P < 0.001). An inverse correlation existed between the decline in HIV-1 RNA levels over 2 to 3 years on nucleoside analogue therapy and the increase over the 10 to 14 days off therapy (Spearman r = -0.53; P = 0.036). Over the 2-week period, a subset of individuals who had genotype testing at multiple reverse transcriptase codons associated with ZDV and 3TC resistance had no changes in genotype off therapy. Nucleoside analogue reverse transcriptase inhibitors may have continued ARV activity despite long durations of partially suppressive therapy and the presence of resistant HIV-1.

Authors
Jr, JJE; Bartlett, JA; Santana, JL; Bellos, NC; Johnson, J; Keller, A; Kuritzkes, DR; Clair, MHS; Johnson, VA
MLA Citation
Jr, JJE, Bartlett, JA, Santana, JL, Bellos, NC, Johnson, J, Keller, A, Kuritzkes, DR, Clair, MHS, and Johnson, VA. "Persistent antiretroviral activity of nucleoside analogues after prolonged zidovudine and lamivudine therapy as demonstrated by rapid loss of activity after discontinuation." Journal of Acquired Immune Deficiency Syndromes 37.5 (2004): 1581-1583.
PMID
15577413
Source
scival
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
37
Issue
5
Publish Date
2004
Start Page
1581
End Page
1583
DOI
10.1097/00126334-200412150-00009

Safety and immunogenicity of a polyvalent peptide C4-V3 HIV vaccine in conjunction with IL-12

We examined the safety and immunogenicity of a human leukocyte antigen-based HIV envelope polyvalent synthetic peptide vaccine, C4-V3, alone and in combination with subcutaneous IL-12 in nine HIV-infected patients. Lymphocyte proliferative responses increased threefold or more to all four peptides at two consecutive post-immunization timepoints for four individuals. Three responders had received IL-12, suggesting a possible adjuvant effect of IL-12. Transient mild injection site reactions (7/9) and systemic symptoms (3/9) occurred.

Authors
Sha, BE; Onorato, M; Bartlett, JA; Bosch, RJ; Aga, E; Nokta, M; Adams, EM; Li, X-D; Eldridge, J; Pollard, RB
MLA Citation
Sha, BE, Onorato, M, Bartlett, JA, Bosch, RJ, Aga, E, Nokta, M, Adams, EM, Li, X-D, Eldridge, J, and Pollard, RB. "Safety and immunogenicity of a polyvalent peptide C4-V3 HIV vaccine in conjunction with IL-12." AIDS 18.8 (2004): 1203-1206.
Source
scival
Published In
AIDS
Volume
18
Issue
8
Publish Date
2004
Start Page
1203
End Page
1206
DOI
10.1097/00002030-200405210-00015

Changes in CD4+ T-cell differentiation phenotype during structured treatment interruption in patients with chronic HIV-1 infection.

Markers of maturation and activation were measured on peripheral CD4+ T cells in chronically HIV-1-infected patients in a randomized, controlled pilot study of structured treatment interruption (STI). Eight subjects underwent 2 cycles of 1 month off and 1 month on highly active antiretroviral therapy (HAART), followed by a final 3-month interruption. During STI, CD4+ T-cell percentage remained relatively stable in 4 of 8 subjects. The remaining 4 STI subjects had significant rapid decline in CD4+ T-cell percentage during STI, followed by return to pre-STI baseline while on HAART. Changes in overall CD4+ T-cell percentage corresponded with fluctuations in the CD45RA+CCR7+ naive and CD45RA-CCR7+ central memory subsets. Subjects with variable CD4+ T-cell percentages tended to have higher pre-HAART plasma HIV-1 RNA set-points and experienced higher levels of plasma HIV-1 RNA rebound during STI. These results suggest that interruptions should be avoided whenever possible in patients on HAART with high plasma HIV-1 RNA set-points.

Authors
Alexander, TH; Ortiz, GM; Wellons, MF; Allen, A; Grace, EJ; Schweighardt, B; Brancato, J; Sandberg, JK; Furlan, SN; Miralles, GD; Nixon, DF; Bartlett, JA
MLA Citation
Alexander, TH, Ortiz, GM, Wellons, MF, Allen, A, Grace, EJ, Schweighardt, B, Brancato, J, Sandberg, JK, Furlan, SN, Miralles, GD, Nixon, DF, and Bartlett, JA. "Changes in CD4+ T-cell differentiation phenotype during structured treatment interruption in patients with chronic HIV-1 infection." J Acquir Immune Defic Syndr 34.5 (December 15, 2003): 475-481.
PMID
14657757
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
34
Issue
5
Publish Date
2003
Start Page
475
End Page
481

Early intensification with abacavir in subjects at high risk for incomplete viral suppression

Authors
Bartlett, JA; Tebas, P; Bassett, R; Huang, W; Kuritzkes, D; Reisler, R; Loyack, N; Robisons, K
MLA Citation
Bartlett, JA, Tebas, P, Bassett, R, Huang, W, Kuritzkes, D, Reisler, R, Loyack, N, and Robisons, K. "Early intensification with abacavir in subjects at high risk for incomplete viral suppression." Antiviral Therapy 8.4 (2003): 361-363.
PMID
14518706
Source
scival
Published In
Antiviral therapy
Volume
8
Issue
4
Publish Date
2003
Start Page
361
End Page
363

Emergence of drug-resistant HIV-1 variants in patients undergoing structured treatment interruptions.

We report the emergence of drug-resistant viral mutations in chronically HIV-infected individual undergoing structured treatment interruptions (STI). THe protease mutations K101E and K103N were detected at the end of the second or third STI. We concluded that the repeated abrupt termination and resumption of certain antiretroviral drug regimens during STI therapy may lead to the development of drug resistance in chronically HIV-infected individuals.

Authors
Schweighardt, B; Ortiz, GM; Grant, RM; Wellons, M; Miralles, GD; Kostrikis, LG; Bartlett, JA; Nixon, DF
MLA Citation
Schweighardt, B, Ortiz, GM, Grant, RM, Wellons, M, Miralles, GD, Kostrikis, LG, Bartlett, JA, and Nixon, DF. "Emergence of drug-resistant HIV-1 variants in patients undergoing structured treatment interruptions." AIDS 16.17 (November 22, 2002): 2342-2344.
PMID
12441810
Source
pubmed
Published In
AIDS
Volume
16
Issue
17
Publish Date
2002
Start Page
2342
End Page
2344

Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis.

Filgrastim, or granulocyte colony-stimulating factor, reverses neutropenia associated with human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) infections. During a trial of anti-CMV retinitis therapies coadministered with antiretroviral therapy, 2-4 plasma specimens of HIV-1 RNA were collected from 36 HIV-1-infected patients receiving filgrastim to prevent neutropenia and from 36 patients not receiving filgrastim. For both groups, the crude mean and mean rate of change of HIV-1 log(10) RNA levels were similar. Adjustment for covariates (CD4(+) T cell lymphocytes, virus load at enrollment, level of neutropenia and antiretroviral therapy [mainly non-highly active antiretroviral therapy], and anti-CMV therapy during follow-up) resulted in a mean log(10) HIV-1 RNA level for individuals receiving filgrastim versus those not receiving the drug of 5.11 versus 4.87 (P=.12) and respective log mean rates of change per month of -0.08 versus -0.21 (P=.08). This latter difference has borderline statistical significance, which suggests that filgrastim may reduce the decline of HIV-1 RNA loads.

Authors
Davidson, M; Min, Y-I; Holbrook, JT; Van Natta, M; Quinn, TC; Murphy, RL; Welch, W; Jabs, DA; Meinert, CL
MLA Citation
Davidson, M, Min, Y-I, Holbrook, JT, Van Natta, M, Quinn, TC, Murphy, RL, Welch, W, Jabs, DA, and Meinert, CL. "Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis." The Journal of infectious diseases 186.7 (October 2002): 1013-1018.
PMID
12232843
Source
epmc
Published In
Journal of Infectious Diseases
Volume
186
Issue
7
Publish Date
2002
Start Page
1013
End Page
1018
DOI
10.1086/342956

Addition of cyclophosphamide to antiretroviral therapy does not diminish the cellular reservoir in HIV-infected persons.

The chronically HIV-infected cellular reservoir in lymphoid tissue (LT) represents a formidable obstacle to the long-term success of antiretroviral therapy. Cytoreductive chemotherapy with cyclophosphamide (CTX) reduces cells in LT, and we hypothesized that coadministration of antiretroviral therapy with CTX may diminish the cellular reservoir over time. Ten antiretroviral treatment-naive subjects were recruited, and they received stavudine, lamivudine and nelfinavir (antiretroviral therapy, ART) until 2 consecutive plasma HIV RNA levels measured < 50 copies/ml (step 1). Five subjects then received ART alone, whereas five subjects received ART plus three escalating doses of CTX (step 2). Viral DNA was measured in LT obtained by excisional lymph node biopsy and peripheral blood mononuclear cells (PBMCs), using quantitative polymerase chain reaction at three time points in both groups (before steps 1 and 2, and after CTX). Viral DNA declined in both groups after the initiation of ART alone in step 1. During step 2 both groups experienced a modest decline compared with step 1. However, no significant differences were observed in viral DNA in LT or PBMCs between the ART alone and the ART plus CTX groups. Suppression of plasma HIV RNA levels < 50 copies/ml was not maintained in the ART plus CTX group, perhaps because of inadequate medication adherence. The group receiving ART plus CTX had lower CD4(+) lymphocyte counts and absolute total lymphocytes compared with the ART alone group. We conclude that the addition of CTX to ART did not diminish the cellular reservoir in HIV-infected persons.

Authors
Bartlett, JA; Miralles, GD; Sevin, AD; Silberman, M; Pruitt, SK; Ottinger, J; Gryszowska, V; Fiscus, SA; Bucy, RP; ACTG 380 Study Team,
MLA Citation
Bartlett, JA, Miralles, GD, Sevin, AD, Silberman, M, Pruitt, SK, Ottinger, J, Gryszowska, V, Fiscus, SA, Bucy, RP, and ACTG 380 Study Team, . "Addition of cyclophosphamide to antiretroviral therapy does not diminish the cellular reservoir in HIV-infected persons." AIDS Res Hum Retroviruses 18.8 (May 20, 2002): 535-543.
PMID
12036483
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
18
Issue
8
Publish Date
2002
Start Page
535
End Page
543
DOI
10.1089/088922202753747888

Protease inhibitors are associated with a slowed progression of HIV-related renal diseases.

AIMS: While angiotensin-con-verting enzyme inhibitors and zidovudine may improve the course of the most common HIV-related renal disease, HIV-associated nephropathy (HIVAN), the effect of anti-retroviral combination therapy on this and other HIV-related renal diseases has not been assessed. This study describes the clinical course of HIV-related renal diseases and the effect of protease inhibitors on their progression. METHODS: This retrospective cohort study reviews the clinical course of 19 patients with a clinical or biopsy-proven diagnosis of HIVAN or other HIV-related renal diseases. Groups progressing and not progressing to ESRD were compared using longitudinal analyses to assess the association between creatinine clearance and clinical and therapeutic factors. RESULTS: The cohort consisted of 16 African-Americans, 2 Caucasians and 1 Native American. Their modes of HIV infection were intravenous drug use (7), a history of men having sex with men (3) and heterosexual behavior (5). Patients were followed for a median of 16.6 months. Seven patients reached ESRD. Loss of creatinine clearance over time did not differ among genders, races, or patients with different modes of HIV infection. Longitudinal analyses demonstrated an association between protease inhibitors and prednisone and a slower decline in creatinine clearance in multivariable models (p = 0.04 and 0.003, respectively). CONCLUSIONS: The epidemiology and clinical course of HIV-related renal diseases is more heterogeneous than previously described. This study suggests a benefit to the use of protease inhibitors and prednisone on the progression of these nephropathies.

Authors
Szczech, LA; Edwards, LJ; Sanders, LL; van der Horst, C; Bartlett, JA; Heald, AE; Svetkey, LP
MLA Citation
Szczech, LA, Edwards, LJ, Sanders, LL, van der Horst, C, Bartlett, JA, Heald, AE, and Svetkey, LP. "Protease inhibitors are associated with a slowed progression of HIV-related renal diseases." Clin Nephrol 57.5 (May 2002): 336-341.
PMID
12036191
Source
pubmed
Published In
Clinical nephrology
Volume
57
Issue
5
Publish Date
2002
Start Page
336
End Page
341

HIV infection: treatment outcomes in older and younger adults.

OBJECTIVES: To determine the effect of antiretroviral therapy (ART) on the immunological and virological outcomes of older human immunodeficiency virus (HIV)-infected patients compared with younger HIV-infected patients. DESIGN: Matched (1:2) retrospective case-control study (1993-1999). SETTING: Duke University Infectious Diseases Clinic. PARTICIPANTS: One hundred one older patients, mean age 56.7 (range 50-79) and 202 younger patients, mean age 32.8 (range 21-39). Patients were matched on baseline CD4+ cell count and date of clinic entry. MEASUREMENTS: The virological and immunological outcomes were viral suppression (HIV ribonucleic acid (RNA) level < or =400 copies/ml) and change in CD4+ cell count. To estimate differences in antiretroviral drug exposure, the percentage of patients on ART overall and by drug class was compared. To assess antiretroviral drug exposure further, the percentage of patients having interruptions in ART was compared. RESULTS: The older and younger groups had similar baseline CD4+ cell counts (332 vs 306 cells/mm3; P =.31) and similar increases in CD4+ cell counts (+3.47 vs +4.60 cells/mm3/month; P =.37) over a mean +/- standard deviation of 2.4 +/- 1.7 years of follow-up. The older group had a higher percentage of patients with current plasma HIV RNA levels less than 400 (46% vs 34%; P =.05). The groups had similar rates of non-nucleoside reverse transcriptase, nucleoside reverse transcriptase, and protease inhibitor use. The older group had fewer interruptions in ART than the younger group (11% vs 26%; P =.01). CONCLUSIONS: Older HIV-infected patients responded well to ART, with a significantly greater percentage achieving a current plasma HIV RNA below detectable limits. Older patients experienced similar increases in CD4+ cell count as younger matched controls. Older patients were less likely to interrupt ART, which suggests better adherence and/or tolerance and may explain the higher rate of HIV RNA suppression.

Authors
Wellons, MF; Sanders, L; Edwards, LJ; Bartlett, JA; Heald, AE; Schmader, KE
MLA Citation
Wellons, MF, Sanders, L, Edwards, LJ, Bartlett, JA, Heald, AE, and Schmader, KE. "HIV infection: treatment outcomes in older and younger adults." J Am Geriatr Soc 50.4 (April 2002): 603-607.
PMID
11982658
Source
pubmed
Published In
Journal of American Geriatrics Society
Volume
50
Issue
4
Publish Date
2002
Start Page
603
End Page
607

Addressing the challenges of adherence.

Adherence to antiretroviral therapy is a crucial determinant of treatment success. Studies have unequivocally demonstrated the close association between adherence and plasma HIV RNA levels, CD4 cell counts, and mortality in patients with HIV infection and disease. Adherence levels of > or =95% are required to maintain virologic suppression. However, actual adherence rates are often far lower; most studies show that 40% to 60% of patients are <90% adherent. Adherence also tends to decrease over time. Patients offer a range of reasons for nonadherence, but the most frequently cited one is simply that they forget; other reasons include being away from home, being busy, or experiencing a change in daily routine. Additional barriers to adherence include psychiatric disorders, such as depression or substance use, uncertainty about the effectiveness of treatment and the consequences of poor adherence, regimen complexity, and treatment side effects. Several strategies can be employed in the effort to support patients' adherence, and all members of the multidisciplinary team should ideally employ these strategies in combination. Efforts should be made to educate and motivate patients, simplify treatment regimens and tailor them to individual lifestyles, prepare for and manage side effects, and address the concrete issues that may be a barrier to adherence. Recruiting an adherence monitor, providing memory aids to medication taking, and anticipating course corrections can also help patients achieve the adherence rates needed for successful treatment of HIV infection and disease.

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "Addressing the challenges of adherence." J Acquir Immune Defic Syndr 29 Suppl 1 (February 1, 2002): S2-10. (Review)
PMID
11832696
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
29 Suppl 1
Publish Date
2002
Start Page
S2
End Page
10

Predictors of proteinuria and renal failure among women with HIV infection.

BACKGROUND: Glomerular disease with proteinuria and renal failure are complications of human immunodeficiency virus (HIV) infection. While studies suggest risk factors for both include black race and lower CD4 lymphocyte count, they have not been established in population-based cohorts. This study examines the risk factors for proteinuria and renal failure in a large cohort of HIV-infected women not selected for the presence of renal disease. METHODS: This prospective cohort includes 2059 women enrolled in the Women's Interagency HIV study (WIHS). WIHS is a longitudinal study of the clinical course of HIV infection in which subjects are followed biannually with a detailed exam including urine analysis, serum creatinine, CD4 lymphocyte count, and HIV RNA level. Proteinuria was defined as > or =+1 on urine dipstick exam on at least two consecutive urine analyses, and renal failure was defined as a doubling of serum creatinine. Multivariable logistic regression was used to estimate the associations between clinical variables and the presence of proteinuria on initial evaluation in a cross-sectional analysis. Cox proportional hazards regression was used to estimate the associations between clinical variables and time to renal failure among study participants with proteinuria in a prospective longitudinal analysis. RESULTS: Of 2057 HIV-positive women, 32% (N=671) had proteinuria on initial evaluation. Predictors of proteinuria include increasing (log) HIV RNA level [odds ratio (OR)=1.05], black race (OR=2.0), absolute CD4 lymphocyte count < or =200 cells/mm3 (OR=1.41), and the presence of hepatitis C antibody (OR=1.27; all P < 0.0001). Absolute CD4 lymphocyte count < or =200 cells/mm3 [hazard ratio (HR)=3.57, P=0.001], detectable HIV RNA level (HR=2.33, P=0.02), increasing systolic blood pressure (HR=1.02, P=0.002), and decreasing albumin (HR=3.33, P=0.0001) and increasing creatinine (1.67, P=0.0001) were all associated with the development of renal failure. CONCLUSIONS: This analysis establishes the associations between both increasing HIV RNA level and decreasing CD4 lymphocyte count with the presence of proteinuria and occurrence of renal failure. Additionally, it demonstrates an association between proteinuria and a positive hepatitis C antibody. To lessen the presence and progression of renal disease among HIV-infected patients, future research should focus on suppression of the HIV RNA level and improvement in CD4 lymphocyte count.

Authors
Szczech, LA; Gange, SJ; van der Horst, C; Bartlett, JA; Young, M; Cohen, MH; Anastos, K; Klassen, PS; Svetkey, LP
MLA Citation
Szczech, LA, Gange, SJ, van der Horst, C, Bartlett, JA, Young, M, Cohen, MH, Anastos, K, Klassen, PS, and Svetkey, LP. "Predictors of proteinuria and renal failure among women with HIV infection." Kidney Int 61.1 (January 2002): 195-202.
PMID
11786101
Source
pubmed
Published In
Kidney international
Volume
61
Issue
1
Publish Date
2002
Start Page
195
End Page
202
DOI
10.1046/j.1523-1755.2002.00094.x

Severity of HIV-associated neuropathy is associated with plasma HIV-1 RNA levels

Objective: To determine if there is an association between plasma HIV-1 RNA levels and severity of HIV-associated distal symmetrical polyneuropathy (DSP). Design: Substudy of AIDS Clinical Trials Group Protocol 291, a double-blind, placebo-controlled study of recombinant human nerve growth factor for the treatment of painful DSP. Methods: Two-hundred and thirty-six subjects had plasma HIV-1 RNA load assayed at baseline. Mean and maximum neuropathic pain was assessed once daily by the Gracely Pain Scale. Other measures included subjects' global pain assessment and quantitative sensory tests (QST). These values were correlated with baseline HIV-1 RNA levels. Results: Among 168 subjects with detectable plasma HIV-1 RNA, there was a significant correlation between plasma HIV-1 RNA and the severity of maximum and global pain, and toe cooling thresholds. Maximum and global pain assessment correlated with plasma HIV-1 RNA in individuals with detectable viral load (r, 0.162 and 0.194; P = 0.04 and 0.01, respectively). Conclusions: There is an association between plasma HIV-1 RNA levels and the severity of pain and QST results in HIV-associated DSP. Further studies are needed to determine if aggressive use of antiretroviral drugs, including the use of dideoxynucleosides, may be of benefit to prevent or improve peripheral neuropathy. © 2002 Lippincott Williams & Wilkins.

Authors
Simpson, DM; Haidich, A-B; Schifitto, G; Yiannoutsos, CT; Geraci, AP; McArthur, JC; Katzenstein, DA; Sacks, H; Khan, A; Gerits, P; Bartlett, J; Maenza, J; Carter, K; Becker, R; Rexrod, V; Cohen, B; Cooper, C; Murphy, R; Phair, J; Berger, JR; Ryan, S; Nath, A; Greenberg, R; Klenner, S; Ryan, M; Reichman, R; Kieburtz, K; Shoemaker, M; Navia, B; Hirsch, M; McCarthy, E; Flynn, T; Adornato, B; Slamowitz, D; Valle, S; Norris, J; Rubin, M; Ponticello, L; Zaprianova, I; Hall, C; Kapoor, C; Horst, CVD et al.
MLA Citation
Simpson, DM, Haidich, A-B, Schifitto, G, Yiannoutsos, CT, Geraci, AP, McArthur, JC, Katzenstein, DA, Sacks, H, Khan, A, Gerits, P, Bartlett, J, Maenza, J, Carter, K, Becker, R, Rexrod, V, Cohen, B, Cooper, C, Murphy, R, Phair, J, Berger, JR, Ryan, S, Nath, A, Greenberg, R, Klenner, S, Ryan, M, Reichman, R, Kieburtz, K, Shoemaker, M, Navia, B, Hirsch, M, McCarthy, E, Flynn, T, Adornato, B, Slamowitz, D, Valle, S, Norris, J, Rubin, M, Ponticello, L, Zaprianova, I, Hall, C, Kapoor, C, and Horst, CVD et al. "Severity of HIV-associated neuropathy is associated with plasma HIV-1 RNA levels." AIDS 16.3 (2002): 407-412.
PMID
11834952
Source
scival
Published In
AIDS
Volume
16
Issue
3
Publish Date
2002
Start Page
407
End Page
412
DOI
10.1097/00002030-200202150-00012

An infected laceration

Authors
Siraj, DS; Bartlett, JA; Hyslop, N
MLA Citation
Siraj, DS, Bartlett, JA, and Hyslop, N. "An infected laceration." Infections in Medicine 19.2 (2002): 63-65.
Source
scival
Published In
Infections in Medicine
Volume
19
Issue
2
Publish Date
2002
Start Page
63
End Page
65

Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy.

The thymus of HIV-seropositive patients can enlarge as CD4+ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define the etiology of the enlargement, the thymuses of two HIV-infected individuals on HAART were biopsied. For more than 3 years before initiation of HAART, both patients (38 and 41 years of age) had documented CD4+ T lymphopenia. Peripheral blood samples were obtained to assess circulating CD4+ CD45RA+ CD62L+ T cells, which were thought to have recently developed in the thymus. Peripheral blood T cells from both patients and thymocytes from the second patient were also tested for levels of DNA episomes formed during T cell receptor gene rearrangement (T cell receptor rearrangement excision circles, TRECs). With HAART, peripheral blood CD4+ T cell counts increased from approximately 60/mm(3) to 552/mm(3) and 750/mm(3) for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD4+ CD45RA+ CD62L+ T cells and quantitation of T cell TRECs also reflected active thymopoiesis in both patients. Thus, in these two HIV-seropositive adults examined after initiation of HAART, thymic enlargement represented active thymopoiesis. Thymopoiesis in adult AIDS patients may contribute to immune reconstitution even after prolonged CD4+ T lymphopenia.

Authors
Markert, ML; Alvarez-McLeod, AP; Sempowski, GD; Hale, LP; Horvatinovich, JM; Weinhold, KJ; Bartlett, JA; D'Amico, TA; Haynes, BF
MLA Citation
Markert, ML, Alvarez-McLeod, AP, Sempowski, GD, Hale, LP, Horvatinovich, JM, Weinhold, KJ, Bartlett, JA, D'Amico, TA, and Haynes, BF. "Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy." AIDS Res Hum Retroviruses 17.17 (November 20, 2001): 1635-1643.
PMID
11779351
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
17
Issue
17
Publish Date
2001
Start Page
1635
End Page
1643
DOI
10.1089/088922201753342040

Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects.

The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4(+) T cells >400 per microl. CD4(+) T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-gamma-producing HIV-1-specific CD8(+) and CD4(+) T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8(+) T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4(+) T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4(+) T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4(+) T cell counts, and showed no enhancement of antiviral CD8(+) T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.

Authors
Ortiz, GM; Wellons, M; Brancato, J; Vo, HT; Zinn, RL; Clarkson, DE; Van Loon, K; Bonhoeffer, S; Miralles, GD; Montefiori, D; Bartlett, JA; Nixon, DF
MLA Citation
Ortiz, GM, Wellons, M, Brancato, J, Vo, HT, Zinn, RL, Clarkson, DE, Van Loon, K, Bonhoeffer, S, Miralles, GD, Montefiori, D, Bartlett, JA, and Nixon, DF. "Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects." Proc Natl Acad Sci U S A 98.23 (November 6, 2001): 13288-13293.
PMID
11687611
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
98
Issue
23
Publish Date
2001
Start Page
13288
End Page
13293
DOI
10.1073/pnas.221452198

Primary care for patients infected with human immunodeficiency virus: a randomized controlled trial.

OBJECTIVE: To measure the impact of a teaching intervention and to compare process and outcomes of care for HIV-infected patients randomly assigned to a general medicine clinic (GMC) or an infectious disease clinic (IDC) for primary care. DESIGN: Prospective, randomized, controlled trial. SETTING: University hospital in Durham, NC. PATIENTS: Two hundred fourteen consecutive HIV-infected patients presenting for primary care. INTERVENTION: Physicians at the GMC received HIV-related training and evidence-based practice guidelines. MEASUREMENTS: Utilization of services, health-related quality of life, preventive and screening measures, and antiretroviral use for one year. RESULTS: At baseline GMC patients were more likely to be African American (85% vs 71%; P =.03) and had lower baseline CD4+ cell counts than IDC patients (262 +/- 269 vs 329 +/- 275; P =.05). A similar and high proportion of patients in both groups received appropriate preventive care services including Pneumocystis carinii pneumonia (PCP) prophylaxis, pneumococcal vaccination, and antiretroviral therapy. Screening for TB was more frequent in GMC (89% vs 68%; P =.001). In the year following randomization, GMC patients made more visits to the emergency department than IDC patients (1.6 +/- 3.0 vs 0.7 +/- 1.5; P =.05). Hospital use was higher for GMC patients with average length of stay 7.8 +/- 6.3 days compared to 5.7 +/- 3.8 days for IDC patients (P =.01). In analyses, which adjust for potential baseline imbalances, these differences remained. CONCLUSIONS: Targeted education in GMC achieved similar provision of primary care for GMC patients, yet use of health care services was higher for this group. The delivery of adequate primary care is necessary but not sufficient to produce changes in health care utilization.

Authors
Keitz, SA; Box, TL; Homan, RK; Bartlett, JA; Oddone, EZ
MLA Citation
Keitz, SA, Box, TL, Homan, RK, Bartlett, JA, and Oddone, EZ. "Primary care for patients infected with human immunodeficiency virus: a randomized controlled trial." J Gen Intern Med 16.9 (September 2001): 573-582.
PMID
11556937
Source
pubmed
Published In
Journal of General Internal Medicine
Volume
16
Issue
9
Publish Date
2001
Start Page
573
End Page
582

Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults.

AIM: To estimate the effectiveness of triple combination therapy in antiretroviral-naive adults. METHODS: A systematic overview of results from clinical trials involving triple combination therapy with dual nucleoside reverse transcriptase inhibitors (NRTI) and: a protease inhibitor (PI triple); a non-nucleoside reverse transcriptase inhibitor (NNRTI triple); or a third NRTI (triple NUC). Data from 23 clinical trials involving 31 independent treatment groups, 19 unique antiretroviral regimens, and 3257 enrolled patients were included in this study. RESULTS: Median log(10) baseline plasma HIV RNA and CD4 cell count over all trials averaged 4.69 (49,329 copies/ml) and 375 x 10(6) cells/l, respectively. The overall estimated percentage of patients with plasma HIV RNA < or = 400 copies/ml at 24 weeks was 64% [95% confidence interval (CI), 60 to 67%]. The percentages of patients with plasma HIV RNA < or = 50 copies/ml at 48 weeks by drug class were: PI triple, 46% (95% CI, 41 to 52%); NNRTI triple, 51% (95% CI, 43 to 59%); triple NUC, 45% (95% CI, 36 to 54%). The CD4 cell count increase over all trials at 24 and 48 weeks averaged +123 x 10(6) cells/l (95% CI, 111 x 10(6) to 135 x 10(6) cells/l) and +160 x 10(6) cells/l (95% CI, 146 x 10(6) to 175 x 10(6) cells/l), respectively and did not differ between drug classes. In multivariable regression analysis, neither baseline plasma HIV RNA level and CD4 cell count nor treatment regimen predicted plasma HIV RNA < or = 50 copies/ml at week 48. However, pill count was significantly negatively associated with plasma HIV RNA < or = 50 copies/ml at week 48 (P = 0.0085). CONCLUSIONS: The results suggest that three drug regimens containing two NRTI with a PI, a NNRTI, or a third NRTI may provide comparable activity, and practical issues such as daily pill burden should be considered when choosing a treatment regimen.

Authors
Bartlett, JA; DeMasi, R; Quinn, J; Moxham, C; Rousseau, F
MLA Citation
Bartlett, JA, DeMasi, R, Quinn, J, Moxham, C, and Rousseau, F. "Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults." AIDS 15.11 (July 27, 2001): 1369-1377.
PMID
11504958
Source
pubmed
Published In
AIDS
Volume
15
Issue
11
Publish Date
2001
Start Page
1369
End Page
1377

Immunologic profile of human immunodeficiency virus-infected patients during viral remission and relapse on antiretroviral therapy.

A dissociation between plasma human immunodeficiency virus (HIV) RNA levels and CD4(+) cell counts has been reported in patients experiencing viral relapse while receiving antiretroviral therapy. This study compared patients with stable CD4(+) lymphocytes during viral relapse while receiving treatment with patients who had sustained virus suppression. Plasma HIV RNA levels, lymphocyte immunophenotyping, and T cell receptor excision circle (TREC) levels were measured. Naive CD4(+) lymphocyte phenotype and TREC levels were not significantly different in patients with virus suppression or in those who had relapsed. However, CD8(+) lymphocyte activation, including the number and percentage of activated cells and CD38 antibody-binding capacity, was significantly elevated during viral relapse, compared with that in suppressed patients. By multivariable regression analyses, CD8(+) and CD4(+) lymphocyte activation were associated significantly with increasing plasma HIV RNA levels.

Authors
Wellons, MF; Ottinger, JS; Weinhold, KJ; Gryszowka, V; Sanders, LL; Edwards, LJ; Gooding, ME; Thomasch, JR; Bartlett, JA
MLA Citation
Wellons, MF, Ottinger, JS, Weinhold, KJ, Gryszowka, V, Sanders, LL, Edwards, LJ, Gooding, ME, Thomasch, JR, and Bartlett, JA. "Immunologic profile of human immunodeficiency virus-infected patients during viral remission and relapse on antiretroviral therapy." J Infect Dis 183.10 (May 15, 2001): 1522-1525.
PMID
11319689
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
183
Issue
10
Publish Date
2001
Start Page
1522
End Page
1525
DOI
10.1086/320193

Meningococcemia in a patient coinfected with hepatitis C virus and HIV.

We describe the first reported case of meningococcemia in a patient coinfected with hepatitis C virus and HIV. Hypocomplementemia secondary to hepatic dysfunction may have enhanced the patient's susceptibility to meningococcal infection.

Authors
Nelson, CG; Iler, MA; Woods, CW; Bartlett, JA; Fowler, VG
MLA Citation
Nelson, CG, Iler, MA, Woods, CW, Bartlett, JA, and Fowler, VG. "Meningococcemia in a patient coinfected with hepatitis C virus and HIV." Emerg Infect Dis 6.6 (November 2000): 646-648.
Website
http://hdl.handle.net/10161/13327
PMID
11076725
Source
pubmed
Published In
Emerging infectious diseases
Volume
6
Issue
6
Publish Date
2000
Start Page
646
End Page
648
DOI
10.3201/eid0606.000615

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

Authors
Markert, ML; Hicks, CB; Bartlett, JA; Harmon, JL; Hale, LP; Greenberg, ML; Ferrari, G; Ottinger, J; Boeck, A; Kloster, AL; McLaughlin, TM; Bleich, KB; Ungerleider, RM; Lyerly, HK; Wilkinson, WE; Rousseau, FS; Heath-Chiozzi, ME; Leonard, JM; Haase, AT; Shaw, GM; Bucy, RP; Douek, DC; Koup, RA; Haynes, BF; Bolognesi, DP; Weinhold, KJ
MLA Citation
Markert, ML, Hicks, CB, Bartlett, JA, Harmon, JL, Hale, LP, Greenberg, ML, Ferrari, G, Ottinger, J, Boeck, A, Kloster, AL, McLaughlin, TM, Bleich, KB, Ungerleider, RM, Lyerly, HK, Wilkinson, WE, Rousseau, FS, Heath-Chiozzi, ME, Leonard, JM, Haase, AT, Shaw, GM, Bucy, RP, Douek, DC, Koup, RA, Haynes, BF, Bolognesi, DP, and Weinhold, KJ. "Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection." AIDS Res Hum Retroviruses 16.5 (March 20, 2000): 403-413.
PMID
10772526
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
16
Issue
5
Publish Date
2000
Start Page
403
End Page
413
DOI
10.1089/088922200309061

Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: A meta-analysis

Objective: To evaluate treatment-mediated changes in HIV-1 RNA and CD4 count as prognostic markers and surrogate end points for disease progression (AIDS/death). Methods: Data from 13,045 subjects in all 16 randomized trials comparing nucleoside analogue reverse transcriptase inhibitors and having HIV-1 RNA measurements at 24 weeks were obtained. A total of 3146 subjects had HIV-1 RNA and CD4 count determinations at 24 weeks after starting treatment. Results: At Week 24, the percentage of subjects experiencing an HIV-1 RNA decrease of >1 log10 copies/ml or a CD4 count increase of >33% was similar (22% vs 25%). Changes in both markers at Week 24 were significant independent predictors of AIDS/death: Across trials, the average reduction in hazard was 51% per 1 log10 HIV-1 RNA copies/ml decrease (95% confidence interval: 41%, 59%) and 20% per 33% CD4 count increase (17%, 24%). In univariate analyses, the hazard ratio for AIDS/death in randomized treatment comparisons was significantly associated with differences between treatments in mean area under the curve of HIV-1 RNA changes to Weeks 8 and 24 (AUCMB) and mean CD4 change at Week 24, but, in multivariate analysis, only mean CD4 change was significant. Conclusions: Change in HIV-1 RNA, particularly using AUCMB, and in CD4 count should be measured to aid patient management and evaluation of treatment activity in clinical trials. However, short-term changes in these markers are imperfect as surrogate end points for long-term clinical outcome because two randomized treatment comparisons may show similar differences between treatments in marker changes but not similar differences in progression to AIDS/death.

Authors
Babiker, A; Bartlett, J; Breckenridge, A; Collins, G; Coombs, R; Cooper, D; Creagh, T; Cross, A; Daniels, M; Darbyshire, J; Dawson, D; DeGruttola, V; DeMasi, R; Dolin, R; Eron, J; Fischl, M; Grossberg, S; Hamilton, J; Hammer, S; Hartigan, P; Henry, K; Hill, A; Hughes, M; Kahn, J; Katlama, C; Katzenstein, D; Kim, S; Mildvan, D; Montaner, J; Moore, M; Neaton, J; O'Brien, W; Ribaudo, H; Richman, D; Saag, M; Salgo, M; Saravolatz, L; Schooley, R; Seligmann, M; Staszewski, S; Struthers, L; Tierney, C et al.
MLA Citation
Babiker, A, Bartlett, J, Breckenridge, A, Collins, G, Coombs, R, Cooper, D, Creagh, T, Cross, A, Daniels, M, Darbyshire, J, Dawson, D, DeGruttola, V, DeMasi, R, Dolin, R, Eron, J, Fischl, M, Grossberg, S, Hamilton, J, Hammer, S, Hartigan, P, Henry, K, Hill, A, Hughes, M, Kahn, J, Katlama, C, Katzenstein, D, Kim, S, Mildvan, D, Montaner, J, Moore, M, Neaton, J, O'Brien, W, Ribaudo, H, Richman, D, Saag, M, Salgo, M, Saravolatz, L, Schooley, R, Seligmann, M, Staszewski, S, Struthers, L, and Tierney, C et al. "Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: A meta-analysis." AIDS Research and Human Retroviruses 16.12 (2000): 1123-1133.
PMID
10954887
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
16
Issue
12
Publish Date
2000
Start Page
1123
End Page
1133
DOI
10.1089/088922200414965

Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials.

Lamivudine population pharmacokinetics were investigated by using nonlinear mixed-effect modelling (NONMEM) analysis of data from 394 human immunodeficiency virus (HIV)-infected patients treated with lamivudine (150 to 300 mg every 12 h) in two large, phase III clinical efficacy-safety trials, NUCA3001 and NUCA3002. Analyses of 1,477 serum lamivudine concentration determinations showed that population estimates for lamivudine oral clearance (CL/F; 25.1 liters/h) and volume of distribution (V/F; 128 liters) were similar to values previously reported for HIV-infected patients in phase I pharmacokinetic studies. Lamivudine CL/F was significantly influenced by the covariates creatinine clearance and weight and not affected by age, Centers for Disease Control and Prevention (CDC) classification, CD4(+) cell count, HIV type 1 (HIV-1) RNA PCR, or gender and race when CL/F was corrected for differences in patient weight. The population estimate for lamivudine V/F was not significantly influenced by the covariates gender, race, age, weight, renal function, HIV-1 RNA PCR, or CDC classification and CD4(+) cell count when creatinine clearance was included with CL/F in the model. Lamivudine disposition was significantly influenced by renal function. However, as only three patients had an estimated creatinine clearance of <60 ml/min, dosage adjustments for patients with impaired renal function should not be determined based on the population parameters derived in this analysis.

Authors
Moore, KH; Yuen, GJ; Hussey, EK; Pakes, GE; Eron, JJ; Bartlett, JA
MLA Citation
Moore, KH, Yuen, GJ, Hussey, EK, Pakes, GE, Eron, JJ, and Bartlett, JA. "Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials." Antimicrob Agents Chemother 43.12 (December 1999): 3025-3029.
PMID
10582904
Source
pubmed
Published In
Antimicrobial agents and chemotherapy
Volume
43
Issue
12
Publish Date
1999
Start Page
3025
End Page
3029

Strategies of antiretroviral therapy in adults.

Recent progress in antiretroviral treatment has led to dramatic improvements in HIV-related morbidity and mortality. These improvements have been fostered by advances in our understanding of HIV-related pathogenesis, the use of plasma HIV RNA levels to monitor patients, and the availability of 13 licensed antiretroviral drugs. Numerous drug combinations, especially those containing three or more agents, can suppress plasma HIV RNA levels below the lower limit of detection in the majority of treated patients. Urologists should be familiar with the limitations of this therapeutic response: patient adherence, drug resistance, a residual burden of chronically infected cells which are refractory to treatment, an unknown impact on HIV in genital secretions, and potential transmissibility through sexual contact.

Authors
Itani, S; Bartlett, JA
MLA Citation
Itani, S, and Bartlett, JA. "Strategies of antiretroviral therapy in adults." Urol Clin North Am 26.4 (November 1999): 809-x. (Review)
PMID
10584621
Source
pubmed
Published In
Urologic Clinics of North America
Volume
26
Issue
4
Publish Date
1999
Start Page
809
End Page
x

Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection.

A key question in understanding the status of the immune system in HIV-1 infection is whether the adult thymus contributes to reconstitution of peripheral T lymphocytes. We analyzed the thymus in adult patients who died of HIV-1 infection. In addition, we studied the clinical course of HIV-1 infection in three patients thymectomized for myasthenia gravis and determined the effect of antiretroviral therapy on CD4(+) T cells. We found that five of seven patients had thymus tissue at autopsy and that all thymuses identified had inflammatory infiltrates surrounding lymphodepleted thymic epithelium. Two of seven patients also had areas of thymopoiesis; one of these patients had peripheral blood CD4(+) T-cell levels of <50/mm3 for 51 months prior to death. Of three thymectomized patients, one rapidly progressed to AIDS, one progressed to AIDS over seven years (normal progressor), whereas the third remains asymptomatic at least seven years after seroconversion. Both latter patients had rises in peripheral blood CD4(+) T cells after antiretroviral therapy. Most patients who died of complications of HIV-1 infection did not have functional thymus tissue, and when present, thymopoiesis did not prevent prolonged lymphopenia. Thymectomy before HIV-1 infection did not preclude either peripheral CD4(+) T-cell rises or clinical responses after antiretroviral therapy.

Authors
Haynes, BF; Hale, LP; Weinhold, KJ; Patel, DD; Liao, HX; Bressler, PB; Jones, DM; Demarest, JF; Gebhard-Mitchell, K; Haase, AT; Bartlett, JA
MLA Citation
Haynes, BF, Hale, LP, Weinhold, KJ, Patel, DD, Liao, HX, Bressler, PB, Jones, DM, Demarest, JF, Gebhard-Mitchell, K, Haase, AT, and Bartlett, JA. "Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection." J Clin Invest 103.4 (February 1999): 453-460.
PMID
10021452
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
103
Issue
4
Publish Date
1999
Start Page
453
End Page
460
DOI
10.1172/JCI5201

Erratum: Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection (The Journal of Clinical Investigation (1999) 103 (453- 460))

Authors
Haynes, BF; Hale, LP; Weinhold, KJ; Patel, DD; Liao, H-X; Bressler, PB; Jones, DM; Demarest, JF; Gebhard-Mitchell, K; Haase, AT; Bartlett, JA
MLA Citation
Haynes, BF, Hale, LP, Weinhold, KJ, Patel, DD, Liao, H-X, Bressler, PB, Jones, DM, Demarest, JF, Gebhard-Mitchell, K, Haase, AT, and Bartlett, JA. "Erratum: Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection (The Journal of Clinical Investigation (1999) 103 (453- 460))." Journal of Clinical Investigation 103.6 (1999): 921--.
Source
scival
Published In
Journal of Clinical Investigation
Volume
103
Issue
6
Publish Date
1999
Start Page
921-

Primary care of HIV infection.

Four cases illustrate some of the issues involved in treating HIV-infected patients in a primary care setting. Primary care physicians are hard-pressed to achieve the same results as infectious disease specialists, yet are increasingly responsible for performing the initial tests, choosing the therapeutic regimen, ensuring the patient's compliance with the regimen, and monitoring the results.

Authors
Bartlett, JA; Sexton, DJ
MLA Citation
Bartlett, JA, and Sexton, DJ. "Primary care of HIV infection." Hosp Pract (1995) 33.12 (December 15, 1998): 53-69.
PMID
9866647
Source
pubmed
Published In
Hospital practice (1995)
Volume
33
Issue
12
Publish Date
1998
Start Page
53
End Page
69

Variability in repeated consecutive measurements of plasma human immunodeficiency virus RNA in persons receiving stable nucleoside reverse transcriptase inhibitor therapy or no treatment.

Plasma human immunodeficiency virus (HIV) RNA levels correlate closely with clinical prognosis in both treated and untreated HIV-infected persons and are widely used to guide clinical practice and as a primary end point in clinical trials. Thus, variability in these measurements may significantly affect their interpretation in clinical practice and research. The variability in consecutive measurements of plasma HIV RNA levels was studied in 387 subjects receiving either stable nucleoside reverse transcriptase inhibitor therapy or no treatment. The Pearson's correlation coefficient between baseline measures 2 weeks apart was 0.92. The mean SD in consecutive measurements 1 month apart was 0.31 log10 copies/mL with a 95% tolerance limit of 0.7 log10 copies/mL (5-fold). Two-thirds of the total variance in consecutive measures 1 month apart was due to biologic fluctuation; one-third was due to assay variance. The biologic variance increased proportionately with the number of weeks between assessments. Clinicians and investigators should be aware of the magnitude of variability in viral RNA levels in the HIV-infected population.

Authors
Bartlett, JA; DeMasi, R; Dawson, D; Hill, A
MLA Citation
Bartlett, JA, DeMasi, R, Dawson, D, and Hill, A. "Variability in repeated consecutive measurements of plasma human immunodeficiency virus RNA in persons receiving stable nucleoside reverse transcriptase inhibitor therapy or no treatment." J Infect Dis 178.6 (December 1998): 1803-1805.
PMID
9815239
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
178
Issue
6
Publish Date
1998
Start Page
1803
End Page
1805

Coadministration of zidovudine and interleukin-2 increases absolute CD4 cells in subjects with Walter Reed stage 2 human immunodeficiency virus infection: results of ACTG protocol 042.

Interleukin-2 (IL-2) can increase numbers of absolute CD4 cells in persons infected with the human immunodeficiency virus who are receiving antiretroviral therapy. Twenty-five subjects with > 400/mm3 absolute CD4 cells received zidovudine and low-dose intravenous or subcutaneous IL-2 (< or = 10(6) U/m2). Absolute CD4 cells increased significantly during IL-2 treatment, and 56% of the subjects achieved a maximal increase of > or = 500 cells/mm3. A dose-response relationship favored increasing IL-2 doses, and subcutaneous delivery offered greater increases than intravenous administration. Fifteen subjects had persistent increases of > or = 100 cells/mm3 6 weeks after IL-2 was discontinued. No changes occurred in delayed-type hypersensitivity or helper T cell responses to recall antigens. Cell-mediated cytotoxicities increased against Daudi cells. IL-2 was well tolerated and only 1 subject required dose reduction. Relatively low-dose IL-2 delivered by subcutaneous or intravenous routes may provide an important complement to antiretroviral therapy to increase absolute CD4 cells with the potential for less toxicity than with higher IL-2 doses.

Authors
Bartlett, JA; Berend, C; Petroni, GR; Ottinger, J; Tyler, DL; Pettinelli, C; Weinhold, KJ
MLA Citation
Bartlett, JA, Berend, C, Petroni, GR, Ottinger, J, Tyler, DL, Pettinelli, C, and Weinhold, KJ. "Coadministration of zidovudine and interleukin-2 increases absolute CD4 cells in subjects with Walter Reed stage 2 human immunodeficiency virus infection: results of ACTG protocol 042." J Infect Dis 178.4 (October 1998): 1170-1173.
PMID
9806053
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
178
Issue
4
Publish Date
1998
Start Page
1170
End Page
1173

Lymphokine-activated killer (LAK) cell anti-HIV-1 ADCC reactivity: a potential strategy for reduction of virus-infected cellular reservoirs.

Lymphocytes from HIV-1-seropositive and -seronegative individuals were examined to determine whether HIV-1 infection interfered with the ability to generate a lymphokine-activated killer (LAK) cell response. Following a 3-day ex vivo incubation in the presence of 1000 U/ml of recombinant interleukin-2, lymphocytes from seropositive individuals exhibited a LAK cell response which was equivalent to or greater than that of seronegative controls as measured against Daudi cell targets. LAK cells from seropositive and seronegative donors showed no specific cytolytic activity against gp120-coated or HIV-1-infected targets. However, in the presence of patient sera, significant levels of virus-specific LAK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) were observed. The level of this specific LAK cell-mediated ADCC was greater than that mediated under similar conditions by freshly isolated peripheral blood mononuclear cells. The greatest improvement in ADCC over baseline activity was seen with lymphocytes from AIDS patients after the 3-day ex vivo activation, suggesting that this patient population might benefit the most from adaptive LAK cell therapy.

Authors
Tyler, DS; Stanley, SD; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Stanley, SD, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "Lymphokine-activated killer (LAK) cell anti-HIV-1 ADCC reactivity: a potential strategy for reduction of virus-infected cellular reservoirs." J Surg Res 79.2 (October 1998): 115-120.
PMID
9758725
Source
pubmed
Published In
Journal of Surgical Research
Volume
79
Issue
2
Publish Date
1998
Start Page
115
End Page
120
DOI
10.1006/jsre.1998.5415

Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative.

OBJECTIVE: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1MN, HIV-1RF, HIV-1EV91, and HIV-1Can0A. DESIGN: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. METHODS: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. RESULTS: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1MN, HIV-1RF, or HIV-1(4489-5) laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). CONCLUSIONS: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infected patients.

Authors
Bartlett, JA; Wasserman, SS; Hicks, CB; Dodge, RT; Weinhold, KJ; Tacket, CO; Ketter, N; Wittek, AE; Palker, TJ; Haynes, BF
MLA Citation
Bartlett, JA, Wasserman, SS, Hicks, CB, Dodge, RT, Weinhold, KJ, Tacket, CO, Ketter, N, Wittek, AE, Palker, TJ, and Haynes, BF. "Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative." AIDS 12.11 (July 30, 1998): 1291-1300.
PMID
9708408
Source
pubmed
Published In
AIDS
Volume
12
Issue
11
Publish Date
1998
Start Page
1291
End Page
1300

A placebo-controlled trial of ranitidine in patients with early human immunodeficiency virus infection.

Previous uncontrolled reports have suggested that H2-antagonists may possess immunomodulatory activity in human immunodeficiency virus (HIV)-infected patients. Such trials reported improvements in HIV-related symptoms, increased absolute CD4 cell numbers, and improvements in other measures of host immunity. The present trial was a randomized, placebo-controlled, double-blind trial of ranitidine 300 mg (orally twice daily) in subjects with early HIV infection (absolute CD4 cells, 400-700/mm3). Eighty-one subjects entered the trial and 73 completed 16 weeks on study medications. There were no significant differences in the time-weighted average change from baseline between the 2 treatment groups in absolute CD4 cell number, plasma HIV RNA level, or most other surrogate markers of HIV infection. Serum beta2-microglobulin levels were significantly lower in placebo than ranitidine recipients. Ranitidine should not be recommended for the treatment of HIV-infected patients unless it is used for established indications.

Authors
Bartlett, JA; Berry, PS; Bockman, KW; Stein, A; Johnson, J; Graham, S; Quinn, J; DeMasi, R; Alexander, WJ
MLA Citation
Bartlett, JA, Berry, PS, Bockman, KW, Stein, A, Johnson, J, Graham, S, Quinn, J, DeMasi, R, and Alexander, WJ. "A placebo-controlled trial of ranitidine in patients with early human immunodeficiency virus infection." J Infect Dis 177.1 (January 1998): 231-234.
PMID
9419196
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
177
Issue
1
Publish Date
1998
Start Page
231
End Page
234

Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen

Objective: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1(MN), and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1(MN), HIV-1(RF), HIV-1(EV91), and HIV-1(Can0A). Design: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. Methods: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 106/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. Results: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1(MN), HIV-1(RF), or HIV-14489-5 laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). Conclusions: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infected patients.

Authors
Bartlett, JA; Wasserman, SS; Hicks, CB; Dodge, RT; Weinhold, KJ; Tacket, CO; Ketter, N; Wittek, AE; Palker, TJ; Haynes, BF
MLA Citation
Bartlett, JA, Wasserman, SS, Hicks, CB, Dodge, RT, Weinhold, KJ, Tacket, CO, Ketter, N, Wittek, AE, Palker, TJ, and Haynes, BF. "Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen." AIDS 12.11 (1998): 1291-1300.
Source
scival
Published In
AIDS
Volume
12
Issue
11
Publish Date
1998
Start Page
1291
End Page
1300

Strategies of Antiretroviral Therapy in Adults.

Recent progress in antiretroviral treatment has led to dramatic improvements in HIV-related morbidity and mortality. These improvements have been fostered by advances in our understanding of HIV-related pathogenesis, the use of plasma HIV RNA levels to monitor patients, and the availability of 11 licensed antiretroviral drugs, including the potent protease inhibitors. Numerous drug combinations, especially those containing three agents, can suppress plasma HIV RNA levels below the lower limit of detection in the majority of treated patients. However, the limitations of this therapeutic response-patient compliance, drug resistance, and a residual burden of chronically infected cells which are refractory to treatment-should be familiar to the oncologist.

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "Strategies of Antiretroviral Therapy in Adults." Oncologist 3.2 (1998): 111-118.
PMID
10388092
Source
pubmed
Published In
The oncologist
Volume
3
Issue
2
Publish Date
1998
Start Page
111
End Page
118

Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy.

In the attempt to develop immunotherapeutic strategies for acquired immunodeficiency syndrome capable of activating effector cells in an antigen-specific manner while maintaining the broadest possible T-cell repertoire, we evaluated two canarypox (ALVAC)-based vectors for their capacity to induce ex vivo activation/expansion of human immunodeficiency virus (HIV)-specific CD8+ cytotoxic lymphocyte precursors (CTLp) obtained from HIV-1-infected donors. These two vectors, vCP205 encoding HIV-1 gp120 + TM (28 amino acid transmembrane anchor sequence) in addition to Gag/protease and vCP300 encoding gp120 + Gag/protease as well as Nef and Pol CTL determinants, are pancytotropic but replication incompetent in mammalian cells. Bulk peripheral blood mononuclear cells (PBMCs) or enriched CD8+ T cells were stimulated for 10 days with autologous ALVAC-infected PBMCs in the presence of different cytokine combinations (interleukin-2 [IL-2], IL-4, IL-7, and IL-12). Activation by ALVAC constructs was highly antigen-specific, because vCP205 elicited only Env and Gag CTL, whereas vCP300 elicited broader reactivities against Env, Gag, Pol, and Nef determinants. The ALVAC activation of CTLp was IL-2 dependent and enhanced by the addition of IL-7, whereas IL-4 and IL-12 failed to augment cytotoxic reactivities elicited by these constructs. The expansion of enriched CD8+ T cells after activation with vCP300 was higher in patients with CD4 counts greater than 400 cells/microL. Two rounds of in vitro stimulation (IVS) with vCP300 resulted in nearly an eightfold expansion of CD8+ lymphocytes over a 25-day period. After the second IVS, an average 3.2-fold increase among the different antigen-specific CTL frequencies was achieved. These studies clearly show that HIV-recombinant ALVAC vectors represent powerful polyvalent antigenic stimuli for activation and expansion of the CD8 lymphocyte response that occurs as a result of HIV infection.

Authors
Ferrari, G; Berend, C; Ottinger, J; Dodge, R; Bartlett, J; Toso, J; Moody, D; Tartaglia, J; Cox, WI; Paoletti, E; Weinhold, KJ
MLA Citation
Ferrari, G, Berend, C, Ottinger, J, Dodge, R, Bartlett, J, Toso, J, Moody, D, Tartaglia, J, Cox, WI, Paoletti, E, and Weinhold, KJ. "Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy." Blood 90.6 (September 15, 1997): 2406-2416.
PMID
9310492
Source
pubmed
Published In
Blood
Volume
90
Issue
6
Publish Date
1997
Start Page
2406
End Page
2416

Central nervous system pneumocystosis in a patient with AIDS.

Extrapulmonary involvement with Pneumocystis carinii has been described in 0.5%-2.5% of persons with AIDS. One hundred nine patients with AIDS and confirmed extrapulmonary pneumocystosis were identified, and seven of these patients (including our patients) had central nervous system (CNS) pneumocystosis. Of these seven patients, six had prior AIDS-related complications, and three had previous P. carinii pneumonia. Six patients had CNS symptoms, one of whom underwent a focal neurological examination. No cases were diagnosed before death. The involved sites were the cerebral cortex (2 patients), meninges (2), pituitary gland (1), putamen (1), and nonspecified locations (3). In two patients, organisms were seen around blood vessels, and in five patients there was concurrent neuropathology. In summary, CNS involvement with P. carinii usually occurs as a late complication of AIDS and probably represents hematogenous dissemination.

Authors
Bartlett, JA; Hulette, C
MLA Citation
Bartlett, JA, and Hulette, C. "Central nervous system pneumocystosis in a patient with AIDS." Clin Infect Dis 25.1 (July 1997): 82-85. (Review)
PMID
9243039
Source
pubmed
Published In
Clinical Infectious Diseases
Volume
25
Issue
1
Publish Date
1997
Start Page
82
End Page
85

Itraconazole maintenance treatment for histoplasmosis in AIDS: A prospective, multicenter trial

Purpose: To study the efficacy and safety of maintenance treatment with itraconazole for disseminated histoplasmosis in patients with AIDS. Patients and Methods: This was a prospective, multicenter, open-label study conducted at university-based hospitals participating in the AIDS Clinical Trial Group (ACTG). Forty-six AIDS patients with mild to moderate disseminated histoplasmosis who had successfully completed 12 weeks of induction treatment with itraconazole were treated with itraconazole, 200 mg once daily (42 patients) or 400 mg once daily (4 patients). Patients were followed at monthly intervals with clinical and laboratory assessment for relapse or toxicity. Primary outcome measures were relapse of histoplasmosis and survival. Secondary outcome measures included drag-limiting toxicity and changes in serum and urine Histoplasma polysaccharaide antigen (HPA) levels. Results: Two patients relapsed during a median follow-up period of 87 weeks. The 1-year relapse-free rate was estimated to be 95.3% (95% CI, 85.3%- 99.7%). One relapse may have been related to poor adherence to treatment and the second to concurrent administration of rifampin. From the start of maintenance treatment, the estimated 1-year survival rate was 73.0% (95% CI, 67.5%-77.9%). Five patients discontinued treatment because of suspected drug toxicity, three of whom had possible or probable hepatotoxicity. Median serum and urine HPA levels declined significantly during treatment. The only patient in whom antigen levels rose >2 U developed clinical relapse 1 week later; antigen levels were unavailable in the other relapsing patient. Conclusions: Itraconazole, 200 mg daily, is effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. It is generally well tolerated, but clinicians should be alert for drug interactions and possible hepatotoxicity.

Authors
Hecht, FM; Wheat, J; Korzun, AH; Hafner, R; Skahan, KJ; Larsen, R; Limjoco, MT; Simpson, M; Schneider, D; Keefer, MC; Clark, R; Lai, KK; Jacobson, JM; Squires, K; Bartlett, JA; Powderly, W
MLA Citation
Hecht, FM, Wheat, J, Korzun, AH, Hafner, R, Skahan, KJ, Larsen, R, Limjoco, MT, Simpson, M, Schneider, D, Keefer, MC, Clark, R, Lai, KK, Jacobson, JM, Squires, K, Bartlett, JA, and Powderly, W. "Itraconazole maintenance treatment for histoplasmosis in AIDS: A prospective, multicenter trial." Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 16.2 (1997): 100-107.
PMID
9358104
Source
scival
Published In
Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association
Volume
16
Issue
2
Publish Date
1997
Start Page
100
End Page
107

Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: A meta-analysis of controlled trials

Objectives: Four randomized double-blind trials have demonstrated that zidovudine/lamivudine (ZDV/3TC) reduces HIV RNA and raises CD4 counts relative to control treatments [ZDV or ZDV/zalcitabine (ddC)]. A meta-analysis of the clinical events in these trials was conducted to determine whether treatment with ZDV/3TC was also associated with a clinical benefit. Design: The four trials, ZDV/3TC versus ZDV (NUCA3001, NUCB3001, NUCB3002) or versus ZDV/ddC (NUCA3002), were run concurrently, using the same doses of ZDV and 3TC. Design: The four trials, ZDV/3TC versus ZDV (NUCA3001, NUCB3001, NUCB3002) or versus ZDV/ddC (NUCA3002), were run concurrently, using the same doses of ZDV and 3TC. Setting: Investigational sites in Europe and North America. Patients: The trials recruited 972 HIV-1-positive, male and female patients aged ≤ 18 years, with CD4 counts of 100-500 cells x 106/l. Two trials were for ZDV-naive patients and two were for ZDV pre-treated patients. Main outcome measures: Progression to first new Centers for Disease Control and Prevention (CDC) B or C event was compared between all ZDV/3TC arms and all control (ZDV, ZDV/ddC) arms. Results: A total of 118 patients progressed to a first new CDC B/C event during the four trials, while 28 progressed to a new CDC C event. Meta-analysis of the trials showed a 49% reduction in progression to new CDC B/C events (relative risk, 0.509; 95% confidence interval, 0.365-0.710; P < 0.0001) and a 66% reduction in progression to new CDC C events (relative risk, 0.344; 95% confidence interval, 0.169-0.700; P = 0.003) for the ZDV/3TC patients relative to the control patients. Reductions in progression to CDC B/C disease were seen in subgroups of naive and pre-treated patients, those with high and low CD4 counts and symptomatic and asymptomatic patients. Conclusions: ZDV/3TC combination treatment delays the progression of CDC B/C disease compared with control treatments. In view of the low incidence of CDC C events, the results for progression to CDC C disease should be interpreted with caution.

Authors
Staszewski, S; Hill, AM; Bartlett, J; Eron, JJ; Katlama, C; Johnson, J; Sawyer, W; McDade, H
MLA Citation
Staszewski, S, Hill, AM, Bartlett, J, Eron, JJ, Katlama, C, Johnson, J, Sawyer, W, and McDade, H. "Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: A meta-analysis of controlled trials." AIDS 11.4 (1997): 477-483.
PMID
9084795
Source
scival
Published In
AIDS
Volume
11
Issue
4
Publish Date
1997
Start Page
477
End Page
483

Correspondence between the effect of zidovudine plus lamivudine on plasma HIV level/CD4 lymphocyte count and the incidence of clinical disease in infected individuals

Objectives: To investigate whether apparently beneficial changes in plasma HIV RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are associated with a corresponding clinical benefit. Methods: For 620 patients in two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV) plasma HIV RNA and CD4 lymphocyte count changes were compared in patients randomized to 3TC plus ZDV and patients randomized to other treatment arms. The effect of therapy on the HIV RNA level and CD4 count was compared with the effect of therapy on clinical endpoints over the same time period. Results: Median baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 x 106/l for CD4 count. During the trial a significantly lower HIV RNA level and higher CD4 count was sustained in the ZDV/3TC group compared with the other group, with a difference in the median area under the curve from baseline per month of follow-up of 0.38 log10 copies/ml HIV RNA and 0.18 log2 x 106/l CD4 cells (P < 0.001 in each case). For patients who were initially asymptomatic or in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4 count was 3.14 [95% confidence interval (Cl), 1.44-6.83] and for a 10-fold higher HIV RNA level was 3.22 (1.20-8.59). The RH of progression to AIDS expected with ZDV/3TC compared with the control treatments, given the observed effects of treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed value was 0.16 (0.03-0.74). After adjustment for HIV RNA and CD4 changes over time the observed RH of progression to AIDS for ZDV/3TC treatment compared with controls was increased to 0.36 and was no longer significant (95% CI, 0.07-1.85). Conclusion: In this analysis of two trials, the effects of ZDV/3TC in reducing plasma HIV RNA and raising peripheral blood CD4 counts were associated with concurrent clinical benefits and the effect of treatment on these markers could account for at least part of the clinical benefits of therapy that were observed.

Authors
Phillips, AN; Eron, J; Bartlett, J; Kuritzkes, DR; Johnson, VA; Gilbert, C; Johnson, J; Keller, A; Hill, AM
MLA Citation
Phillips, AN, Eron, J, Bartlett, J, Kuritzkes, DR, Johnson, VA, Gilbert, C, Johnson, J, Keller, A, and Hill, AM. "Correspondence between the effect of zidovudine plus lamivudine on plasma HIV level/CD4 lymphocyte count and the incidence of clinical disease in infected individuals." AIDS 11.2 (1997): 169-175.
PMID
9030363
Source
scival
Published In
AIDS
Volume
11
Issue
2
Publish Date
1997
Start Page
169
End Page
175
DOI
10.1097/00002030-199702000-00006

Lamivudine plus zidovudine compared with zalcitabine plus zidovudine in patients with HIV infection. A randomized, double-blind, placebo-controlled trial. North American HIV Working Party.

OBJECTIVE: To compare the safety and activity of lamivudine plus zidovudine with the safety and activity of zalcitabine plus zidovudine in patients with moderately advanced human immunodeficiency virus (HIV) infection who had received zidovudine. DESIGN: A multicenter, randomized, double-blind, three-arm, 24-week study with a blinded extension through at least 52 weeks. SETTING: 21 sites in the United States, Canada, and Puerto Rico. PATIENTS: 254 patients who had received zidovudine (median duration of previous therapy, 20 months) and had absolute CD4+ cell counts of 100 to 300 cells/mm3. INTERVENTIONS: Patients were randomly assigned to receive one of three regimens: 150 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (low-dose lamivudine group); 300 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (high-dose lamivudine group); or 0.75 mg of zalcitabine plus 200 mg of zidovudine three times daily (zalcitabine group). MEASUREMENTS: Immunologic activity was assessed primarily by changes in absolute CD4+ cell counts; virologic activity was assessed by changes in plasma HIV RNA levels as measured by reverse transcriptase polymerase chain reaction. Safety of the treatment regimens was assessed through the reporting of adverse events. RESULTS: 78% of patients completed 24 weeks of study treatment, and 63% of patients completed 52 weeks of study treatment. Changes in absolute CD4+ cell counts were significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm3 in the low-dose lamivudine group, +23.33 cells/mm3 in the high-dose lamivudine group, and -29.58 cells/mm3 in the zalcitabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log10 copies/mL in the low-dose lamivudine group, -0.51 log10 copies/mL in the high-dose lamivudine group, and -0.39 log10 copies/mL in the zalcitabine group). No significant differences in safety were seen among the three regimens, although the low-dose lamivudine regimen appeared to be better tolerated than the others. CONCLUSIONS: In patients with HIV infection who had previously received zidovudine, 150 mg of lamivudine plus zidovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine plus zidovudine and was better tolerated than 300 mg of lamivudine plus zidovudine.

Authors
Bartlett, JA; Benoit, SL; Johnson, VA; Quinn, JB; Sepulveda, GE; Ehmann, WC; Tsoukas, C; Fallon, MA; Self, PL; Rubin, M
MLA Citation
Bartlett, JA, Benoit, SL, Johnson, VA, Quinn, JB, Sepulveda, GE, Ehmann, WC, Tsoukas, C, Fallon, MA, Self, PL, and Rubin, M. "Lamivudine plus zidovudine compared with zalcitabine plus zidovudine in patients with HIV infection. A randomized, double-blind, placebo-controlled trial. North American HIV Working Party." Ann Intern Med 125.3 (August 1, 1996): 161-172.
PMID
8686973
Source
pubmed
Published In
Annals of internal medicine
Volume
125
Issue
3
Publish Date
1996
Start Page
161
End Page
172

Differentiation of central nervous system lesions in AIDS patients using positron emission tomography (PET).

To determine if positron emission tomography (PET) imaging using F-18 fluorodeoxyglucose (FDG) can accurately distinguish between malignant and infectious central nervous system (CNS) mass lesions in patients with human immunodeficiency virus (HIV) infection, a prospective case series of 18 patients with HIV infection and focal CNS lesions on computed tomography (CT) or magnetic resonance (MR) scans was analysed. The patients were divided into 3 groups based on biopsy results, serology and response to therapy. Group 1 consisted of 8 patients with infectious lesions (4 with toxoplasmosis, 2 with neurosyphilis, 2 with progressive multifocal leukoencephalopathy (PML)). Group 2 consisted of 5 patients with biopsy proven CNS lymphoma. Group 3 consisted of 5 patients with presumed CNS lymphoma. Patients underwent FDG-PET studies as an adjunctive diagnostic procedure. The metabolic activity of each patient's lesion was graded using both a qualitative visual score and a semi-quantitative count ratio comparing the lesion with contralateral brain. CNS lesions diagnosed as lymphomas had statistically higher visual scores (P = 0.001) and count ratios (P = 0.002) than CNS lesions diagnosed as infections. FDG-PET could accurately differentiate lymphoma from infections in 16 of 18 cases. Two cases of PML had high metabolic activity and could not be differentiated from lymphoma. FDG-PET shows great promise in differentiating lymphoma from infectious lesions in the CNS of patients with HIV infection. If larger prospective studies confirm this impression, more specific and rapid treatment of CNS lesions could be performed and perhaps obviate the need for brain biopsy in many cases.

Authors
Heald, AE; Hoffman, JM; Bartlett, JA; Waskin, HA
MLA Citation
Heald, AE, Hoffman, JM, Bartlett, JA, and Waskin, HA. "Differentiation of central nervous system lesions in AIDS patients using positron emission tomography (PET)." Int J STD AIDS 7.5 (August 1996): 337-346.
PMID
8894823
Source
pubmed
Published In
International Journal of STD & AIDS
Volume
7
Issue
5
Publish Date
1996
Start Page
337
End Page
346
DOI
10.1258/0956462961918239

Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.

Authors
Heald, AE; Hsyu, PH; Yuen, GJ; Robinson, P; Mydlow, P; Bartlett, JA
MLA Citation
Heald, AE, Hsyu, PH, Yuen, GJ, Robinson, P, Mydlow, P, and Bartlett, JA. "Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction." Antimicrob Agents Chemother 40.6 (June 1996): 1514-1519.
PMID
8726029
Source
pubmed
Published In
Antimicrobial agents and chemotherapy
Volume
40
Issue
6
Publish Date
1996
Start Page
1514
End Page
1519

Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy.

OBJECTIVE: To examine the impact of continuous versus intermittent fluconazole therapy on fungal colonization and fluconazole resistance in the oropharynx of HIV-infected patients. DESIGN: Case-control study. SETTING: Duke University Adult Infectious Diseases Clinic, a tertiary referral center in North Carolina which provides care for 700 HIV-infected persons. PATIENTS: Nineteen HIV-infected patients on daily continuous fluconazole for a minimum of 6 months and eleven HIV-infected patients on intermittent fluconazole for a minimum of 6 months were matched by sex and CD4 cell count to HIV-infected patients who had not received fluconazole in the preceding 6 months. MAIN OUTCOME MEASURES: Fungal isolation and fluconazole susceptibility testing were performed on oral saline rinses from each patient. RESULTS: The patients taking continuous fluconazole were more likely than matched controls to have had sterile mouth rinses (14 out of 19 versus five out of 19; P < 0.001), and the yeasts that were isolated were more likely than matched controls to be non-Candida albicans species and to have minimum inhibitory concentrations (MIC) to fluconazole > or = 16 micrograms/ml. None of these isolates were associated with symptoms. In contrast, none of the patients in the intermittent fluconazole group had sterile cultures. When this group was compared to controls, they were more likely to have had non-C. albicans species, and the C. albicans isolates obtained had higher MIC to fluconazole. CONCLUSIONS: Long-term continuous therapy with fluconazole may prevent the appearance of Candida in the oral cavity. This finding may reduce recurrence rates and might favorably impact on the clinical appearance of mucosal candidiasis with resistant C. albicans.

Authors
Heald, AE; Cox, GM; Schell, WA; Bartlett, JA; Perfect, JR
MLA Citation
Heald, AE, Cox, GM, Schell, WA, Bartlett, JA, and Perfect, JR. "Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy." AIDS 10.3 (March 1996): 263-268.
PMID
8882665
Source
pubmed
Published In
AIDS
Volume
10
Issue
3
Publish Date
1996
Start Page
263
End Page
268

Lymphoma of the pituitary gland: An unusual presentation of central nervous system lymphoma in AIDS

Authors
Gottfredsson, M; Oury, TD; Bernstein, C; Carpenter, C; Bartlett, JA
MLA Citation
Gottfredsson, M, Oury, TD, Bernstein, C, Carpenter, C, and Bartlett, JA. "Lymphoma of the pituitary gland: An unusual presentation of central nervous system lymphoma in AIDS." American Journal of Medicine 101.5 (1996): 563-564.
PMID
8948282
Source
scival
Published In
American Journal of Medicine
Volume
101
Issue
5
Publish Date
1996
Start Page
563
End Page
564
DOI
10.1016/S0002-9343(96)00257-4

Safety and pharmacokinetics of 5-chloro-2',3'-dideoxy-3'-fluorouridine (935U83) following oral administration of escalating single doses in human immunodeficiency virus-infected adults

5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83) is a nucleoside analog reverse transcriptase inhibitor that has demonstrated selective anti-human immunodeficiency virus (HIV) activity in vitro and favorable safely profiles in monkeys and mice. A phase I study was conducted to evaluate the safety and pharmacokinetics of six escalating single oral doses of 935U83 in 12 HIV- infected adults. The effect of a high-fat meal on the oral bioavailability of 935U83 was also assessed. The volunteers enrolled had CD4+ cell counts ranging from <50 to 753 cells per mm3 (median, 198). In the dose range of 100 to 1,500 mg, 935U83 was well tolerated by all subjects with no drug- related adverse events reported. No significant clinical or laboratory abnormalities were observed throughout the study. 935U83 was rapidly and well absorbed following oral administration with peak plasma concentrations (C(max)) occurring at 0.8 to 1.3 h postdosing. Mean C(max) and AUC(0-∞) values of 935U83 were nearly dose proportional in the 100- to 1,500-mg dose range (from 2.4 to 30 μg/ml and from 3.4 to 59 h · μg/ml, respectively). Elimination of 935U83 from the plasma was rapid, with an apparent half-life of 1.3 to 1.7 h which was independent of the dose level. Administration of 935U83 with a high-fat meal decreased the rate of 935U83 absorption (mean C(max) decreased by ~50% and mean time to C(max) increased by ~1 h) but did not affect the extent of oral bioavailability (AUC(0-∞)) of 935U83. The 5'- O-glucuronide conjugate was the principal metabolite of 935U83 and was present in the plasma of fall volunteers at concentrations lower than 935U83. The molar AUC(0-∞) ratio (935U83 glucuronide to the parent compound) was similar across all dose levels (mean, 21 to 27%). At least 60% of the 935U83 dose was absorbed, and approximately an equal percentage of the dose (30%) was excreted as unchanged 935U83 and as 935U83 glucuronide. Systemic exposure to 935U83 at levels exceeding its average in vitro antiretroviral 50% inhibitory concentration (~0.5 μg/ml or 1.8 μM) can be achieved after a single oral dose.

Authors
Riddler, SA; Wang, LH; Bartlett, JA; Savina, PM; Packard, MV; Mcmahon, DK; Blum, MR; Dunn, JA; Elkins, MM; Mellors, JW
MLA Citation
Riddler, SA, Wang, LH, Bartlett, JA, Savina, PM, Packard, MV, Mcmahon, DK, Blum, MR, Dunn, JA, Elkins, MM, and Mellors, JW. "Safety and pharmacokinetics of 5-chloro-2',3'-dideoxy-3'-fluorouridine (935U83) following oral administration of escalating single doses in human immunodeficiency virus-infected adults." Antimicrobial Agents and Chemotherapy 40.12 (1996): 2842-2847.
PMID
9124852
Source
scival
Published In
Antimicrobial agents and chemotherapy
Volume
40
Issue
12
Publish Date
1996
Start Page
2842
End Page
2847

Antiretroviral monotherapy in early stage human immunodeficiency virus disease has no detectable effect on virus load in peripheral blood and lymph nodes

Initiation of antiretroviral monotherapy early in the course of infection with human immunodeficiency virus may result in a temporary slowing in the rate of disease progression; however, little is known about the virologic effects of early therapy. Virus load was measured in peripheral blood and lymph nodes from 16 antiretroviral-naive patients with a mean CD4 T lymphocyte count of 659 cells/μL at baseline and after 8 weeks of either no treatment or zidovudine therapy. CD4 T lymphocyte counts and all virologic parameters examined remained unchanged regardless of zidovudine treatment status. Histopathology and virus distribution within lymph nodes remained constant between baseline and week 8 in each patient, indicating that the virologic and histologic parameters examined in a single lymph node are representative of a systemic process. Early antiretroviral monotherapy with zidovudine had no effect on virologic parameters in this group of patients with relatively high CD4 T lymphocyte counts and low measures of virus load at baseline.

Authors
Cohen, OJ; Pantaleo, G; Holodniy, M; Fox, CH; Orenstein, JM; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, GN; Lalezari, J; Bartlett, JA; Steigbigel, RT; Cohn, J; Novak, R; McMahon, D; Bilello, J; Fauci, AS
MLA Citation
Cohen, OJ, Pantaleo, G, Holodniy, M, Fox, CH, Orenstein, JM, Schnittman, S, Niu, M, Graziosi, C, Pavlakis, GN, Lalezari, J, Bartlett, JA, Steigbigel, RT, Cohn, J, Novak, R, McMahon, D, Bilello, J, and Fauci, AS. "Antiretroviral monotherapy in early stage human immunodeficiency virus disease has no detectable effect on virus load in peripheral blood and lymph nodes." Journal of Infectious Diseases 173.4 (1996): 849-856.
PMID
8603962
Source
scival
Published In
Journal of Infectious Diseases
Volume
173
Issue
4
Publish Date
1996
Start Page
849
End Page
856

HIV-1 RNA levels and the development of clinical disease

Objective: To assess the prognostic value of HIV RNA levels for predicting clinical disease independently of the CD4 lymphocyte count in patients on antiretroviral therapy. Design: Cohort of HIV-infected patients from two trials of lamivudine therapy. Patients: For 620 patients randomized in the North American NUCA3001 and NUCA3002 trials of lamivudine, HIV RNA levels were measured (median, seven measures per patient) and CD4 counts were assessed at a central laboratory (median, 13 counts per patient). Patients were in the 1993 Centers for Disease Control and Prevention (CDC) stages A (n = 439), B (n = 135) or C (n = 46) at baseline. Outcome measures: For patients who were in CDC stage A at baseline we considered the ability of HIV RNA levels and CD4 counts to predict the development of CDC stage B or C disease. A Cox proportional hazards model was used. In a second analysis, patients who were AIDS-free at baseline were considered, and the endpoint was AIDS (CDC stage C). Results: Patients' initial CD4 counts ranged (5-95% centiles) from 104 to 529 x 10 6/l (median, 274 x 10 6/l) and HIV RNA levels from 1900 to 339 680 copies/ml (median, 44 240 copies/ml). For the first analysis, with CDC stage B or C disease as endpoint, both the most recent HIV RNA level and CD4 count predicted the development of clinical disease [relative hazard (RH) for HIV RNA, 1.96 per 10-fold difference in HIV RNA; 95% confidence interval (CI), 1.41-2.73; P = 0.0001; and RH for CD4 count, 1.82 per twofold difference in CD4 count; 95% CI, 1.27-2.56; P = 0.0009]. When both HIV RNA and CD4 count were included in a multiple regression model, both markers provided information additional to that given by the other (RH for HIV RNA, 1.75; 95% CI, 1.23-2.50; P = 0.002; and RH for CD4 count, 1.40; 95% CI, 0.95-2.07; P = 0.09). In the second analysis, with AIDS as endpoint, both HIV RNA level (P = 0.02) and CD4 count (P = 0.004) were independently associated with clinical progression. These results were essentially unchanged after adjustment for treatment arm (zidovudine/lamivudine versus control arms). Conclusion: The HIV RNA level shows ability to predict the development of clinical disease and may thus be of importance in addition to the CD4 count in patient monitoring.

Authors
Phillips, AN; Eron, JJ; Bartlett, JA; Rubin, M; Johnson, J; Price, S; Self, P; Hill, AM
MLA Citation
Phillips, AN, Eron, JJ, Bartlett, JA, Rubin, M, Johnson, J, Price, S, Self, P, and Hill, AM. "HIV-1 RNA levels and the development of clinical disease." AIDS 10.8 (1996): 859-865.
PMID
8828743
Source
scival
Published In
AIDS
Volume
10
Issue
8
Publish Date
1996
Start Page
859
End Page
865

IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp).

CD8+ cytotoxic T lymphocytes are an important component in the immunologic control of human viral diseases. IL-7, a stromal cell-derived cytokine, has been demonstrated to enhance both anti-tumour and anti-viral CTL as well as lymphokine-activated killer (LAK) activity. We studied the ability of IL-7 to support the activation and the growth of in vitro antigen-specific CTL precursors (CTLp) present in peripheral blood mononuclear cells (PBMC) from HIV-infected patients. Results from these studies demonstrate that inclusion of IL-7 in a vaccinia/HIV-1 vector-based stimulation strategy greatly augmented overall CTL reactivities, whereas addition of IL-7 to unstimulated cultures failed to induce any significant anti-viral cytolytic activity. In four of six patients, HIV-specific lytic activities were significantly higher in cultures stimulated with antigen plus IL-7 compared with in vitro stimulation (IVS) with antigen alone. Cytotoxic activity was principally mediated by CD8+ effector cells, and CD3+/CD8+ cell expansion was increased by 2.7-fold in the presence of IL-7. In PBMC from seronegative donors, IL-7 enhanced anti-vaccinia CTL activities with less effect on cell proliferation. Furthermore, anti-gag CTL frequencies determined by limiting dilution analysis were increased by 2- and 10-fold in two asymptomatic patients following IVS plus IL-7 compared with antigen stimulation alone. Cytofluorimetric analysis revealed that IL-7 preferentially expanded CD8 memory cells (CD45RO+) and CD8+ lymphocytes expressing activation molecules. IL-7 was also able to support the growth of CD4+ lymphocytes, while having no effect on natural killer (NK)/K lymphocytes. Taken together, these data suggest that IL-7 acts cooperatively with the antigen supporting in vitro maturation of CTLp into functional cytotoxic effectors. Thus IL-7 may be an important biologic entity to consider as part of future immune-based therapies in which ex vivo expansion of antigen-driven CTL is an important determinant.

Authors
Ferrari, G; King, K; Rathbun, K; Place, CA; Packard, MV; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Ferrari, G, King, K, Rathbun, K, Place, CA, Packard, MV, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp)." Clin Exp Immunol 101.2 (August 1995): 239-248.
PMID
7544247
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
101
Issue
2
Publish Date
1995
Start Page
239
End Page
248

Taste and smell losses in HIV infected patients.

Human immunodeficiency virus (HIV-1) associated wasting is an increasingly common clinical manifestation of AIDS. The pathogenesis of wasting is multifactorial and includes reduced caloric intake as a major contributing mechanism. The perceptions of taste and smell play an important role in stimulating caloric intake and in optimizing nutrient absorption through cephalic phase reflexes. The purpose of this study was to evaluate the degree of losses in taste and smell function that occur in subjects infected with HIV. Taste and smell function was evaluated in 40 HIV infected individuals and 40 healthy control subjects matched for age, sex, race, smoking behavior, and number of years of education. Chemosensory tests administered to subjects included taste and smell detection thresholds, taste and smell memory tests, taste and smell discrimination tests, and taste and smell identification tasks. Significant differences were observed between experimental and control subjects in glutamic acid taste detection threshold (p < 0.001), quinine hydrochloride taste detection threshold (p < 0.001), menthol smell detection threshold (p < 0.001) and in the taste identification task (p = 0.006). Overall the results suggest abnormalities in the peripheral and central nervous systems, and subjective distortion of taste and smell. A significant correlation was not established between CDC classification of HIV infection and taste and smell function, although trends were observed suggesting worsening function with progression of HIV disease. These results document significant taste and smell losses in HIV infected subjects which may be of clinical significance in the development or progression of HIV associated wasting.

Authors
Graham, CS; Graham, BG; Bartlett, JA; Heald, AE; Schiffman, SS
MLA Citation
Graham, CS, Graham, BG, Bartlett, JA, Heald, AE, and Schiffman, SS. "Taste and smell losses in HIV infected patients." Physiol Behav 58.2 (August 1995): 287-293.
PMID
7568432
Source
pubmed
Published In
Physiology & Behavior
Volume
58
Issue
2
Publish Date
1995
Start Page
287
End Page
293

USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: disease-specific recommendations. USPHS/IDSA Prevention of Opportunistic Infections Working Group.

MLA Citation
"USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: disease-specific recommendations. USPHS/IDSA Prevention of Opportunistic Infections Working Group." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 21 Suppl 1 (August 1995): S32-S43.
PMID
8547510
Source
epmc
Published In
Clinical Infectious Diseases
Volume
21 Suppl 1
Publish Date
1995
Start Page
S32
End Page
S43

Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome

PURPOSE: Amphotericin B has been the treatment of choice for disseminated histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). Oral antifungal agents would be welcome alternatives to standard treatment of disseminated histoplasmosis in less severe cases. The purpose of this study was to assess the efficacy and safety of itraconazole therapy in patients with AIDS and disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial conducted in university hospitals of the AIDS Clinical Trial Group. All patients had AIDS and first episodes of disseminated histoplasmosis. Patients with central nervous system involvement or with severe clinical manifestations were excluded. Patients were treated with itraconazole BID by mouth 300 mg for 3 days and then 200 mg BID for 12 weeks. Resolution of clinical findings, clearance of positive cultures, and drug tolerance were the main outcome measurements. A secondary objective was effect of therapy on Histoplasma capsulatum var capsulatum antigen levels. RESULTS: Of 59 evaluable patients, 50 (85%) responded to therapy. Five patients withdrew because of progressive infection, 1 died of a presumed pulmonary embolus within the first week of therapy without improvement, 2 withdrew because of toxicity, and 1 was lost to follow-up after week 2 of therapy. Patients with moderately severe clinical (fever >39.5°C or Karnofsky score <60) or laboratory abnormalities (alkaline phosphatase >5 times normal or albumin <3 g/dL) at baseline tended to respond more poorly than did other patients. Resolution of complaints of fever and improvement in fatigue occurred after a median of 3 and 6 weeks, respectively, and weight gain after 2 weeks. Fungemia cleared after a median of 1 week. H capsulatum var capsulatum antigen cleared from the urine and serum at rates of 0.2 and 0.3 units per week, respectively. CONCLUSIONS: Itraconazole is safe and effective induction therapy for mild disseminated histoplasmosis in patients with AIDS, offering an alternative to amphotericin B in such cases. Patients with moderately severe or severe histoplasmosis should first be treated with amphotericin B and then may be switched to itraconazole after achieving clinical improvement.

Authors
Wheat, J; Hafner, R; Korzun, AH; Limjoco, MT; Spencer, P; Larsen, RA; Hecht, FM; Powderly, W; Simpson, M; Skahan, KJ; al, E
MLA Citation
Wheat, J, Hafner, R, Korzun, AH, Limjoco, MT, Spencer, P, Larsen, RA, Hecht, FM, Powderly, W, Simpson, M, Skahan, KJ, and al, E. "Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome." American Journal of Medicine 98.4 (1995): 336-342.
PMID
7709945
Source
scival
Published In
American Journal of Medicine
Volume
98
Issue
4
Publish Date
1995
Start Page
336
End Page
342
DOI
10.1016/S0002-9343(99)80311-8

The predictive value of changes in serologic and cell markers of HIV activity for subsequent clinical outcome in patients with asymptomatic HIV disease treated with zidovudine

Objective: To determine if serologic marker responses to zidovudine treatment during the first year of antiretroviral therapy could predict subsequent HIV disease progression independently of absolute CD4 lymphocyte responses. Methods: We conducted a case-control study in patients with asymptomatic HIV disease, who were initiating zidovudine therapy in a randomized, prospective trial. A total of 102 patients who progressed to AIDS or advanced AIDS-related complex and 177 randomly selected controls matched by baseline CD4 cell count and duration of follow-up had serum samples (from prior to and at 8, 16, 32 and 48 weeks of zidovudine treatment) assayed for acid-disassociated HIV p24 antigen, β2-microglobulin (β2M), neopterin, soluble interleukin (IL)-2 receptor, soluble CD4 protein and soluble CD8 protein. Results: Median time to event for cases was 20.2 months; median follow-up on study was 35.4 months for controls. After controlling for absolute CD4 count at baseline, increased baseline serum concentrations of HIV p24 antigen, β2M, neopterin, and soluble IL-2 receptor were highly predictive of increased risk of HIV disease progression. In a multiple logistic regression model, controlling for baseline marker values, change in β2M consistently added independent value to change in CD4 count in predicting subsequent risk of disease progression. Conclusions: Monitoring serum immunologic markers, in particular β2M, in addition to absolute CD4 lymphocyte counts prior to and within the first 4 months after initiating dideoxynucleoside therapy can increase the accuracy of estimations of subsequent long-term risk of clinical HIV disease progression. This information may be useful to clinicians and patients who are making decisions about initiating or changing antiretroviral therapy.

Authors
Jacobson, MA; Gruttola, VD; Reddy, M; Arduino, J-M; Strickland, S; Reichman, RC; Bartlett, JA; Phair, JP; Hirsch, MS; Collier, AC; Soeiro, R; Volberding, P
MLA Citation
Jacobson, MA, Gruttola, VD, Reddy, M, Arduino, J-M, Strickland, S, Reichman, RC, Bartlett, JA, Phair, JP, Hirsch, MS, Collier, AC, Soeiro, R, and Volberding, P. "The predictive value of changes in serologic and cell markers of HIV activity for subsequent clinical outcome in patients with asymptomatic HIV disease treated with zidovudine." AIDS 9.7 (1995): 727-734.
PMID
7546418
Source
scival
Published In
AIDS
Volume
9
Issue
7
Publish Date
1995
Start Page
727
End Page
734

Health reform in the private sector: initiatives of the American Managed Behavioral Healthcare Association.

Authors
Harbin, HT; Shusterman, A; Shaffer, I; Bartlett, J
MLA Citation
Harbin, HT, Shusterman, A, Shaffer, I, and Bartlett, J. "Health reform in the private sector: initiatives of the American Managed Behavioral Healthcare Association." Behavioral healthcare tomorrow 4.5 (1995): 37-39.
PMID
10156223
Source
scival
Published In
Behavioral healthcare tomorrow
Volume
4
Issue
5
Publish Date
1995
Start Page
37
End Page
39

Herpes virus infections, HIV, and disease progression. Guarded optimism.

Authors
Bartlett, J
MLA Citation
Bartlett, J. "Herpes virus infections, HIV, and disease progression. Guarded optimism." AIDS clinical care 7.2 (1995): [d]15-.
PMID
12212538
Source
scival
Published In
AIDS clinical care
Volume
7
Issue
2
Publish Date
1995
Start Page
[d]15

Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue

Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for ≥6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 106 mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue.

Authors
Cohen, OJ; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, GN; Lalezari, J; Bartlett, JA; Steigbigel, RT; Cohn, J; Novak, R; Mcmahon, D; Fauci, AS
MLA Citation
Cohen, OJ, Pantaleo, G, Holodniy, M, Schnittman, S, Niu, M, Graziosi, C, Pavlakis, GN, Lalezari, J, Bartlett, JA, Steigbigel, RT, Cohn, J, Novak, R, Mcmahon, D, and Fauci, AS. "Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue." Proceedings of the National Academy of Sciences of the United States of America 92.13 (1995): 6017-6021.
PMID
7597072
Source
scival
Published In
Proceedings of the National Academy of Sciences of USA
Volume
92
Issue
13
Publish Date
1995
Start Page
6017
End Page
6021
DOI
10.1073/pnas.92.13.6017

Facing the challenge of HIV. Primary care physicians have an obligation to care for those infected.

Authors
Keitz, SA; Bartlett, JA
MLA Citation
Keitz, SA, and Bartlett, JA. "Facing the challenge of HIV. Primary care physicians have an obligation to care for those infected." N C Med J 55.10 (October 1994): 468-470.
PMID
7800057
Source
pubmed
Published In
North Carolina Medical Journal
Volume
55
Issue
10
Publish Date
1994
Start Page
468
End Page
470

Effect of simultaneous didanosine administration on itraconazole absorption in healthy volunteers.

STUDY OBJECTIVE: To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole. DESIGN: Randomized, crossover, unblinded single-dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15. SETTING: A university medical center. PATIENTS: Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash. INTERVENTIONS: Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. MEASUREMENTS AND MAIN RESULTS: Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration-time curve. A mean +/- SD peak serum itraconazole concentration of 0.90 +/- 0.30 micrograms/ml was observed at 3.0 +/- 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI. CONCLUSIONS: Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently.

Authors
May, DB; Drew, RH; Yedinak, KC; Bartlett, JA
MLA Citation
May, DB, Drew, RH, Yedinak, KC, and Bartlett, JA. "Effect of simultaneous didanosine administration on itraconazole absorption in healthy volunteers." Pharmacotherapy 14.5 (September 1994): 509-513.
PMID
7997384
Source
pubmed
Published In
Pharmacotherapy
Volume
14
Issue
5
Publish Date
1994
Start Page
509
End Page
513

Pharmacokinetics and safety of levofloxacin in patients with human immunodeficiency virus infection.

Levofloxacin, the bacteriologically active isomer of ofloxacin, has microbiologic activity against many pathogens common in human immunodeficiency virus (HIV)-infected patients, including Mycoplasma species which may be cofactors in the progression of HIV disease. The purpose of this phase I, double-blind, randomized (1:1), placebo-controlled trial was to evaluate the pharmacokinetics and safety of levofloxacin hemihydrate in 10 asymptomatic HIV-infected males. Plasma concentrations by chiral high-performance liquid chromatography (HPLC) were evaluated for 48 h after a single 350-mg oral dose, at morning predose during the multiple-dosing phase, and for 72 h at steady state after a week of 350 mg every 8 h orally. Mean +/- standard deviation levofloxacin pharmacokinetic parameters (by noncompartmental moment method) after multiple dosing were as follows: area under the concentration-time curve, 31.24 +/- 5.60 mg.h/liter; apparent total body clearance, 11.18 +/- 1.76 liters/h; renal clearance, 8.63 +/- 2.82 liters/h; steady-state volume of distribution, 104.10 +/- 12.48 liters; and effective half-life, 6.50 +/- 0.51 h. Single-dose parameters were not significantly different from the multiple-dose parameters, with the exception of peak concentrations in plasma, which were 4.79 +/- 1.00 and 6.92 +/- 1.56 mg/liter for single- and multiple-dose data, respectively. Essentially identical parameter values were obtained from curve-fitting analysis when the entire 13-day plasma concentration profiles of the subjects were analyzed simultaneously by a two-compartmental distribution model. Levofloxacin pharmacokinetics in HIV-infected patients remained linear upon multiple dosing. The dosing regimen studied provides levels in plasma and urine well above those found to be effective in vitro against pathogens common in HIV-infected patients. Levofloxacin was well- tolerated in this group of asymptomatic HIV-infected males: there were no statistically significant differences in adverse effects in the two groups (P = 0.22). Use of placebo control helped to differentiate disease-related adverse effects from those related to the study drug.

Authors
Goodwin, SD; Gallis, HA; Chow, AT; Wong, FA; Flor, SC; Bartlett, JA
MLA Citation
Goodwin, SD, Gallis, HA, Chow, AT, Wong, FA, Flor, SC, and Bartlett, JA. "Pharmacokinetics and safety of levofloxacin in patients with human immunodeficiency virus infection." Antimicrob Agents Chemother 38.4 (April 1994): 799-804.
PMID
8031049
Source
pubmed
Published In
Antimicrobial agents and chemotherapy
Volume
38
Issue
4
Publish Date
1994
Start Page
799
End Page
804

The duration of zidovudine benefit in persons with asymptomatic HIV infection: Prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group

Objective. - To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry CD4+ cell count. Design and Interventions. - Extended follow-up data from subjects participating in protocol 019 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine's effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo. Setting. - University-based and university-affiliated AIDS research clinics participating in AIDS Clinical Trials Group protocol 019. Patients. - A total of 1565 asymptomatic HIV-infected subjects with entry CD4+ cell counts less than 0.50x109/L (500/μL). Main Outcome Measure. - Time to progression to AIDS or death. Results. - During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P=.008, .004, .007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P=.002, .08, .04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry CD4+ cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo. Conclusions. - Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished over time especially in subjects with entry CD4+ cell counts less than 0.30x109/L (300/μL). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored.

Authors
Volberding, PA; Lagakos, SW; Grimes, JM; Stein, DS; Jr, HHB; Reichman, RC; Bartlett, JA; Hirsch, MS; Phair, JP; Mitsuyasu, RT; Fischl, MA; Soeiro, R
MLA Citation
Volberding, PA, Lagakos, SW, Grimes, JM, Stein, DS, Jr, HHB, Reichman, RC, Bartlett, JA, Hirsch, MS, Phair, JP, Mitsuyasu, RT, Fischl, MA, and Soeiro, R. "The duration of zidovudine benefit in persons with asymptomatic HIV infection: Prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group." Journal of the American Medical Association 272.6 (1994): 437-442.
PMID
7913730
Source
scival
Published In
JAMA : the journal of the American Medical Association
Volume
272
Issue
6
Publish Date
1994
Start Page
437
End Page
442
DOI
10.1001/jama.272.6.437

Cryptosporidium spread in a group residential home [3]

Authors
Heald, AE; Bartlett, JA; Sears, CL; Newman, RD; Guerrant, RL
MLA Citation
Heald, AE, Bartlett, JA, Sears, CL, Newman, RD, and Guerrant, RL. "Cryptosporidium spread in a group residential home [3]." Annals of Internal Medicine 121.6 (1994): 467-468.
PMID
8053626
Source
scival
Published In
Annals of Internal Medicine
Volume
121
Issue
6
Publish Date
1994
Start Page
467
End Page
468

Early versus delayed zidovudine in the management of HIV infection

The controversy surrounding the use of early versus delayed zidovudine therapy has created a contentious debate among clinical investigators, practitioners and their patients. The theoretical basis for antiretroviral therapy derives from the importance of chronic viral replication, especially in lymphoid tissues, throughout the course of HIV infection. Zidovudine has been evaluated in patients with early to middle stages of HIV infection in eight randomised double-blind placebo-controlled trials. Although the trials differ in length of follow-up, zidovudine dosage and endpoint definitions, five conclusions are apparent from a review of their results: early zidovudine does not improve length of survival over delayed zidovudine, early zidovudine results in a transient (one to two years) delay in progression to AIDS, early zidovudine results in a delay in the onset of symptomatic HIV disease, early zidovudine alters surrogate markers for HIV in a favourable direction, and early zidovudine is well tolerated. These clinical benefits of early zidovudine prescription support its use in clinical practice, especially in conjunction with improving strategies of clinical management for patients who deteriorate after receiving early zidovudine. Ultimately combinations of antiretroviral agents may prove most clinically effective and control the emergence of drug resistant isolates from a large viral reservoir in lymphoid tissues.

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "Early versus delayed zidovudine in the management of HIV infection." Expert Opinion on Investigational Drugs 3.8 (1994): 809-819.
Source
scival
Published In
Expert Opinion on Investigational Drugs
Volume
3
Issue
8
Publish Date
1994
Start Page
809
End Page
819

CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism.

HIV-1 infection evokes a vigorous antiviral response that may participate in resolving the initial peak of plasma viremia and maintenance of the asymptomatic state. CD8+ T lymphocytes of HIV-1-infected individuals play a critical role in the cellular anti-HIV response. In agreement with previous reports, we observed a potent suppressive effect on HIV-1 production from autologous CD4+ T lymphocytes by CD8+ T lymphocytes from asymptomatic HIV-1-infected individuals. To elucidate the mechanism(s) of the nonlytic suppressive antiviral activity, we examined the effect of CD8+ T lymphocytes on the transcriptional activity of the HIV-1 promoter (HIV-LTR). CD8+ lymphocytes from HIV-1-infected asymptomatic individuals suppressed tat-mediated HIV-LTR transcription in CD4+ lymphocytes. HIV-LTR transcriptional activity was suppressed by CD8 lymphocytes to an extent similar to tat-mediated transcription whereas CMV immediate early gene promoter activity was not affected. In contrast to the suppressive effect seen with CD8+ lymphocytes from HIV-1-infected individuals, CD8+ lymphocytes from uninfected individuals did not significantly inhibit tat-mediated or HIV-LTR transcription. The transcriptional inhibitory activity was not MHC class I restricted and could be mediated by a soluble factor(s). Supernatants from some CD8+ T lymphocyte cultures from HIV-1+ individuals exerted an inhibitory effect on tat-mediated HIV-LTR transcription comparable to that seen with CD8+ cells. In conclusion, CD8+ lymphocytes from asymptomatic HIV-1+ individuals could suppress virus production by inhibiting HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Chen, CH; Weinhold, KJ; Bartlett, JA; Bolognesi, DP; Greenberg, ML
MLA Citation
Chen, CH, Weinhold, KJ, Bartlett, JA, Bolognesi, DP, and Greenberg, ML. "CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism." AIDS Res Hum Retroviruses 9.11 (November 1993): 1079-1086.
PMID
8312050
Source
pubmed
Published In
AIDS Research and Human Retroviruses
Volume
9
Issue
11
Publish Date
1993
Start Page
1079
End Page
1086
DOI
10.1089/aid.1993.9.1079

Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1.

Yeast strains isolated from the oropharynx of 87 consecutive patients infected with human immunodeficiency virus type 1 were examined for in vitro susceptibility to fluconazole. Candida albicans was isolated from 73 patients. Fifty-one patients had received antifungal therapy in the month preceding the yeast infection. Thirty-two patients had symptomatic oropharyngeal candidiasis. The MICs were correlated with azole use and with clinical symptoms and signs. Although there is overlap between groups, in vitro testing identified a large group of patients for whose yeast isolates the fluconazole MICs were high and who remained symptomatic while receiving azole therapy. This study supports the ability of in vitro testing to predict the clinical outcome of mucosal fungal infections. The study also demonstrates that azole resistance of oropharyngeal yeasts is a common problem in patients infected with human immunodeficiency virus type 1 and that this azole resistance has clinical relevance.

Authors
Cameron, ML; Schell, WA; Bruch, S; Bartlett, JA; Waskin, HA; Perfect, JR
MLA Citation
Cameron, ML, Schell, WA, Bruch, S, Bartlett, JA, Waskin, HA, and Perfect, JR. "Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1." Antimicrob Agents Chemother 37.11 (November 1993): 2449-2453.
PMID
8285632
Source
pubmed
Published In
Antimicrobial agents and chemotherapy
Volume
37
Issue
11
Publish Date
1993
Start Page
2449
End Page
2453

Progress in the understanding of HIV infection: an overview.

The worldwide epidemic of human immunodeficiency virus (HIV) infection will likely be considered the most important public health event of the twentieth century. During the past 15 years, a wealth of information relating to the epidemiology, diagnosis, natural history, and treatment of HIV infection has accumulated. This article details the recent progress in each of these areas.

Authors
Myers, SA; Prose, NS; Bartlett, JA
MLA Citation
Myers, SA, Prose, NS, and Bartlett, JA. "Progress in the understanding of HIV infection: an overview." J Am Acad Dermatol 29.1 (July 1993): 1-21. (Review)
PMID
8315063
Source
pubmed
Published In
Journal of The American Academy of Dermatology
Volume
29
Issue
1
Publish Date
1993
Start Page
1
End Page
21

CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: A novel antiviral mechanism

HIV-1 infection evokes a vigorous antiviral response that may participate in resolving the initial peak of plasma viremia and maintenance of the asymptomatic state. CD8+ T lymphocytes of HIV-1-infected individuals play a critical role in the cellular anti-HIV response. In agreement with previous reports, we observed a potent suppressive effect on HIV-1 production from autologous CD4+ T lymphocytes by CD8+ T lymphocytes from asymptomatic HIV- 1-infected individuals. To elucidate the mechanism(s) of the nonlytic suppressive antiviral activity, we examined the effect of CD8+ T lymphocytes on the transcriptional activity of the HIV-1 promoter (HIV-LTR). CD8+ lymphocytes from HIV-1-infected asymptomatic individuals suppressed tat- mediated HIV-LTR transcription in CD4+ lymphocytes. HIV-LTR transcriptional activity was suppressed by CD8 lymphocytes to an extent similar to tat- mediated transcription whereas CMV immediate early gene promoter activity was not affected. In contrast to the suppressive effect seen with CD8+ lymphocytes from HIV-1-infected individuals, CD8+ lymphocytes from uninfected individuals did not significantly inhibit tat-mediated or HIV-LTR transcription. The transcriptional inhibitory activity was not MHC class I restricted and could be mediated by a soluble factor(s). Supernatants from some CD8+ T lymphocyte cultures from HIV-1+ individuals exerted an inhibitory effect on tat-mediated HIV-LTR transcription comparable to that seen with CD8+ cells. In conclusion, CD8+ lymphocytes from asymptomatic HIV-1+ individuals could suppress virus production by inhibiting HIV-1 gene expression. This suppressive effect of CD8+ T lymphocytes on HIV-1 promoter activity could play a role in the regulation of HIV-1 replication during the asymptomatic period of HIV-1 infection.

Authors
Chen, C-H; Weinhold, KJ; Bartlett, JA; Bolognesi, DP; Greenberg, ML
MLA Citation
Chen, C-H, Weinhold, KJ, Bartlett, JA, Bolognesi, DP, and Greenberg, ML. "CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: A novel antiviral mechanism." AIDS Research and Human Retroviruses 9.11 (1993): 1079-1086.
Source
scival
Published In
AIDS Research and Human Retroviruses
Volume
9
Issue
11
Publish Date
1993
Start Page
1079
End Page
1086

Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of human blood monocytes and peritoneal macrophages.

The influence of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of freshly isolated normal human peritoneal macrophages and blood monocytes was examined. Each of 14 HIV antibody-positive human serum samples was found to block the infection of four virus isolates (human T-cell lymphotropic virus type IIIBa-L [HTLV-IIIBa-L], HTLV-IIIB, D.U. 6587-7, and D.U. 7887-8) at serum dilutions ranging from 10(-1) to 10(-2). Three of these isolates (HTLV-IIIBa-L, D.U. 6587-7, and D.U. 7887-8) infected cultures of monocytes and macrophages rapidly and produced high levels of virus reverse transcriptase and p24 antigen. A fourth virus isolate (HTLV-IIIB) infected the monocytes and macrophages more slowly and produced low levels of viral protein. More dilute HIV antibody-positive sera had no significant effect on the overall level or rate of virus infection or expression. Complement did not appear to influence the course of infection by any combination of antisera or virus examined. Successful HIV-1 infection of the peritoneal macrophages and blood monocytes under the conditions tested showed strict dependence on CD4 since a recombinant CD4 polypeptide and an anti-CD4 monoclonal antibody effectively blocked the process.

Authors
Shadduck, PP; Weinberg, JB; Haney, AF; Bartlett, JA; Langlois, AJ; Bolognesi, DP; Matthews, TJ
MLA Citation
Shadduck, PP, Weinberg, JB, Haney, AF, Bartlett, JA, Langlois, AJ, Bolognesi, DP, and Matthews, TJ. "Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of human blood monocytes and peritoneal macrophages." J Virol 65.8 (August 1991): 4309-4316.
PMID
1712861
Source
pubmed
Published In
Journal of virology
Volume
65
Issue
8
Publish Date
1991
Start Page
4309
End Page
4316

The effect of AZT on in vitro lymphokine-activated killer (LAK) activity in human immunodeficiency virus type-1 (HIV-1) infected individuals.

Human immunodeficiency virus type-1 (HIV-1)-infected individuals exhibit functional impairment in various forms of cell-mediated cytotoxicities (CMC) at all stages of disease. The purpose of this study was to determine (i) if peripheral blood mononuclear cells (PBMC) obtained from HIV-1-infected patients could be stimulated in vitro to yield lymphokine-activated killer (LAK) activity; (ii) if non-MHC-restricted gp120-specific CMC could be preserved; and (iii) what effect zidovudine (AZT) would have on LAK activity. Fourteen asymptomatic HIV-1 seropositive adults and five healthy seronegative adults (controls) were evaluated. PBMCs were isolated and incubated in media or supplemented with IL-2 for 4 or 72 hr. Lysis of the NK resistant target cell line, Daudi, was similar for the control and experimental group. The increase in activity after stimulation was elevated to a similar degree in both seronegative and seropositive groups (P less than 0.001). LAK activity was significantly decreased (P = 0.011) when AZT was added to LAK cultures. In addition, virus production may not have been completely inhibited by AZT in LAK cultures. Thus, PBMCs from asymptomatic HIV-1-infected patients could be stimulated to yield LAK activity. However, AZT can impair LAK generation. It is unclear if LAK activation results in virus production that cannot be inhibited by AZT in this system. Further definition in other patient populations is required prior to applying this information to clinical trials.

Authors
Stine, KC; Tyler, DS; Stanley, SD; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Stine, KC, Tyler, DS, Stanley, SD, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "The effect of AZT on in vitro lymphokine-activated killer (LAK) activity in human immunodeficiency virus type-1 (HIV-1) infected individuals." Cell Immunol 136.1 (August 1991): 165-172.
PMID
1905587
Source
pubmed
Published In
Cellular Immunology
Volume
136
Issue
1
Publish Date
1991
Start Page
165
End Page
172

Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome.

Cryptococcosis is a common opportunistic infection in patients with AIDS. Meningitis is the most frequent manifestation of infection with Cryptococcus neoformans; pneumonia due to this organism, though less frequently recognized, is also a significant entity. A retrospective review was performed of all patients seen at Duke University Medical Center between January 1981 and July 1989 who were infected with both human immunodeficiency virus type 1 and C. neoformans. Of 31 patients with these concomitant infections, 12 had cryptococcal pneumonia (10 definite and two presumptive cases). Eleven of these 12 patients had evidence of extrapulmonary cryptococcal disease as well. Chest radiography showed interstitial infiltrates in 11 instances. For ten of the 12 patients, pulmonary cultures were positive for C. neoformans. Bronchoalveolar lavage fluid from all five patients who underwent bronchoscopy yielded the organism. Acute-phase mortality from cryptococcosis was 42% among patients with pneumonia. Cryptococcal pneumonia in patients with AIDS is probably more common than has previously been recognized and typically presents as interstitial disease that may mimic other opportunistic infections.

Authors
Cameron, ML; Bartlett, JA; Gallis, HA; Waskin, HA
MLA Citation
Cameron, ML, Bartlett, JA, Gallis, HA, and Waskin, HA. "Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome." Rev Infect Dis 13.1 (January 1991): 64-67.
PMID
2017634
Source
pubmed
Published In
Reviews of Infectious Diseases
Volume
13
Issue
1
Publish Date
1991
Start Page
64
End Page
67

Amplification of human immunodeficiency virus provirus from cerebrospinal fluid: Results of long-term clinical follow-up [2]

Authors
Shaunak, S; Albright, RE; Bartlett, JA
MLA Citation
Shaunak, S, Albright, RE, and Bartlett, JA. "Amplification of human immunodeficiency virus provirus from cerebrospinal fluid: Results of long-term clinical follow-up [2]." Journal of Infectious Diseases 164.4 (1991): 818--.
PMID
1894945
Source
scival
Published In
Journal of Infectious Diseases
Volume
164
Issue
4
Publish Date
1991
Start Page
818-

Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS: A randomized, double-blind, placebo-controlled, multicenter study

We randomized 389 symptomatic patients with human immunodeficiency virus (HIV) infection to ditiocarb sodium (400 mg/m2 orally for 24 weeks) or a placebo. Patients were well balanced according to Centers for Disease Control (CDC) group, CD4+ cell number, and duration of disease prior to entry. Ten new acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections occurred in the treated patients and 21 in the controls. Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12). The size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to Pneumocystis carinii pneumonia who was not strictly CDC-defined (RR, 0.46), or when considering as new opportunistic infections three events, which were clinically active at entry, but for which the definitive diagnosis was made during study (RR, 0.49). The administration of ditiocarb did not induce any major adverse clinical or biological reactions. We conclude that, in this study, ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic HIV infection.

Authors
Hersh, EM; Brewton, G; Abrams, D; Bartlett, J; Galpin, J; Gill, P; Gorter, R; Gottlieb, M; Jonikas, JJ; Landesman, S; Levine, A; Marcel, A; Petersen, EA; Whiteside, M; Zahradnik, J; Negron, C; Boutitie, F; Caraux, J; Dupuy, J-M; Salmi, LR
MLA Citation
Hersh, EM, Brewton, G, Abrams, D, Bartlett, J, Galpin, J, Gill, P, Gorter, R, Gottlieb, M, Jonikas, JJ, Landesman, S, Levine, A, Marcel, A, Petersen, EA, Whiteside, M, Zahradnik, J, Negron, C, Boutitie, F, Caraux, J, Dupuy, J-M, and Salmi, LR. "Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS: A randomized, double-blind, placebo-controlled, multicenter study." Journal of the American Medical Association 265.12 (1991): 1538-1544.
PMID
1671884
Source
scival
Published In
Journal of the American Medical Association
Volume
265
Issue
12
Publish Date
1991
Start Page
1538
End Page
1544

Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease

Objectives. - To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine- treated patients with advanced human immunodeficiency virus (HIV) disease. Design. - Prospective observational study. Setting. - Hospital and private clinics in 12 metropolitan centers. Patients. - The study included 754 non- Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. Outcome Measures. - Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. Results. - At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4 + counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P=.01; Hispanic vs white, P=.32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P=.0001; Hispanic vs white, P=.86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P=.03; Hispanic vs white, P=.09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4 + counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. Conclusions. - Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis.

Authors
Easterbrook, PJ; Keruly, JC; Creagh-Kirk, T; Richman, DD; Chaisson, RE; Moore, RD; Bartlett, J; Link, G; McAvinue, S; Bryson, Y; al, E
MLA Citation
Easterbrook, PJ, Keruly, JC, Creagh-Kirk, T, Richman, DD, Chaisson, RE, Moore, RD, Bartlett, J, Link, G, McAvinue, S, Bryson, Y, and al, E. "Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease." Journal of the American Medical Association 266.19 (1991): 2713-2718.
Source
scival
Published In
JAMA : the journal of the American Medical Association
Volume
266
Issue
19
Publish Date
1991
Start Page
2713
End Page
2718
DOI
10.1001/jama.266.19.2713

Current and future treatment of HIV infection.

After much frustration in the last decade, HIV therapeutics is an emerging discipline. Over the past few years a number of new agents have been evaluated, including such antiviral drugs as zidovudine, dideoxycytidine and dideoxyinosine, and immunomodulators such as alpha interferon and interleukin-2. The author discusses these and other agents and the prospects for combination therapy.

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "Current and future treatment of HIV infection." Oncology (Williston Park) 4.11 (November 1990): 19-29. (Review)
PMID
2150323
Source
pubmed
Published In
Oncology
Volume
4
Issue
11
Publish Date
1990
Start Page
19
End Page
29

Simultaneous pneumococcal and Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome.

Authors
Ingram, CW; Bartlett, JA
MLA Citation
Ingram, CW, and Bartlett, JA. "Simultaneous pneumococcal and Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome." South Med J 83.10 (October 1990): 1215-1217.
PMID
2218665
Source
pubmed
Published In
Southern Medical Journal
Volume
83
Issue
10
Publish Date
1990
Start Page
1215
End Page
1217

Amplification of HIV-1 provirus from cerebrospinal fluid and its correlation with neurologic disease.

The polymerase chain reaction (PCR) was used to detect human immunodeficiency virus type 1 (HIV-1) proviral sequences (gag and env) in nucleated cells from the cerebrospinal fluid (CSF) of 31 HIV-1-positive patients, and the results were compared with clinical and radiologic evidence of neurologic disease. Provirus was detected in 21 patients, of whom 20 had neurologic abnormalities. Provirus was not detected in another 6, all of whom were neurologically normal. No neurologic disease has developed in 4 of these 6 patients for whom 12.8 months of follow-up is available. PCR of CSF nucleated cells from HIV-positive patients provides early, rapid, direct evidence of neurologic involvement.

Authors
Shaunak, S; Albright, RE; Klotman, ME; Henry, SC; Bartlett, JA; Hamilton, JD
MLA Citation
Shaunak, S, Albright, RE, Klotman, ME, Henry, SC, Bartlett, JA, and Hamilton, JD. "Amplification of HIV-1 provirus from cerebrospinal fluid and its correlation with neurologic disease." J Infect Dis 161.6 (June 1990): 1068-1072.
PMID
2189004
Source
pubmed
Published In
Journal of Infectious Diseases
Volume
161
Issue
6
Publish Date
1990
Start Page
1068
End Page
1072

Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection. Humoral and cellular defects.

HIV-1-specific cell-mediated cytotoxicity (CMC) is a form of antibody-dependent cellular cytotoxicity (ADCC) in which HIV-1-specific antibodies arm NK cells directly to become cytotoxic for targets bearing HIV-1 antigenic determinants. This non-MHC-restricted cytotoxic activity is present in early stages of disease and declines markedly with disease progression. To understand the cellular and humoral factors contributing to the reduction in this activity, the conditions under which maximal arming of cells occurs was examined in vitro. With the use of a large patient cohort, a strong positive correlation was found between the capacity of a serum to direct lysis in standard ADCC assays and its ability to arm NK cells. Patients with minimal HIV-1-specific ADCC-directing antibodies exhibited low levels of CMC and were unable to arm normal effector cells in vitro. The lack of sufficient ADCC-directing antibodies was found to be one cause of defective CMC in some patients. Unlike asymptomatics, only a weak positive correlation was found between arming and ADCC with sera from AIDS patients, indicating that a factor other than absolute HIV-1 specific antibody titer was responsible for decreased CMC in this patient population. Another group of patients was found to have diminished CMC despite the presence of antibodies in the serum that were fully capable of arming normal effector cells to become cytotoxic for gp120-expressing targets. When compared with those of normal individuals, lymphocytes from seropositive patients mediated significantly reduced levels of cytotoxicity in ADCC and arming assays with the use of a high titered HIV-1-specific serum. In both assay systems, the magnitude and frequency of dysfunction in antibody-dependent cytolysis was found to be greater among AIDS patients than among asymptomatic individuals. The demonstration of both cellular and humoral defects in the ability of seropositive individuals to manifest ADCC reactivities strongly suggests that HIV-1 infection may significantly compromise the effectiveness of this potentially important cytolytic reactivity in vivo.

Authors
Tyler, DS; Stanley, SD; Nastala, CA; Austin, AA; Bartlett, JA; Stine, KC; Lyerly, HK; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Stanley, SD, Nastala, CA, Austin, AA, Bartlett, JA, Stine, KC, Lyerly, HK, Bolognesi, DP, and Weinhold, KJ. "Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection. Humoral and cellular defects." J Immunol 144.9 (May 1, 1990): 3375-3384.
PMID
2329275
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
144
Issue
9
Publish Date
1990
Start Page
3375
End Page
3384

HIV testing in North Carolina.

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "HIV testing in North Carolina." N C Med J 51.4 (April 1990): 150-151.
PMID
2333108
Source
pubmed
Published In
North Carolina Medical Journal
Volume
51
Issue
4
Publish Date
1990
Start Page
150
End Page
151

HIV-1-associated thrombocytopenia. The role of splenectomy.

Thrombocytopenic purpura is a common hematologic abnormality occurring in individuals infected with the human immunodeficiency virus, HIV-1. Of the nearly two million people infected with HIV-1, approximately 11% have platelet counts of less than 100,000/mm3. If no etiology other than HIV-1 infection can be found for the thrombocytopenia, the syndrome is referred to as HIV-1-associated thrombocytopenia (HAT). Steroids lead to an improvement in the platelet count in 60% to 80% of effected individuals but the majority of those who respond cannot maintain a normal platelet count when steroids are withdrawn. Furthermore concern over chronic steroid therapy in HIV-1-infected individuals has led to the investigation of other forms of treatment for this syndrome. This report describes the experience at Duke University Medical Center with eight patients who developed HAT and subsequently underwent splenectomy. In this group there was 1 complete response, 5 partial responses, and 2 patients who did not respond. There were no perioperative deaths and minimal perioperative morbidity. No evidence for the progression of HIV-1 infection in asymptomatic patients after splenectomy to AIDS related complex (ARC) or to the acquired immune deficiency syndrome (AIDS) was seen. In addition no increase in the susceptibility to infections by encapsulated organisms as a result of splenectomy was observed after a mean follow-up of 13.25 months. A review of 79 other cases reported in the literature suggests a higher response rate than that observed in our patients. Reasons for this discrepancy are discussed and an algorithm defining the role of splenectomy in the management of HAT is presented.

Authors
Tyler, DS; Shaunak, S; Bartlett, JA; Iglehart, JD
MLA Citation
Tyler, DS, Shaunak, S, Bartlett, JA, and Iglehart, JD. "HIV-1-associated thrombocytopenia. The role of splenectomy." Ann Surg 211.2 (February 1990): 211-217. (Review)
PMID
2405794
Source
pubmed
Published In
Annals of Surgery
Volume
211
Issue
2
Publish Date
1990
Start Page
211
End Page
217

HIV-associated autoimmune hemolytic anemia: report of a case and review of the literature.

While anemia and a positive direct anti-globulin test are each frequently observed in the clinical syndrome of human immunodeficiency virus (HIV) infection, autoimmune hemolytic anemia has rarely been reported in this setting. A case of severe warm autoimmune hemolytic anemia (AIHA) with reticulocytopenia in a patient with AIDS-related complex is reported. Laboratory and clinical findings of severe hemolysis were present, including anhaptoglobinemia, microspherocytosis, splenomegaly, and transfusion dependence. Azidothymidine (AZT) therapy may have exacerbated this patient's anemia. Splenectomy produced a delayed but complete remission of the AIHA despite continuation of AZT therapy. Review of other reports of positive direct antiglobulin tests and autoimmune hemolytic anemia in patients with HIV infections suggests that autoantibodies may be a significant cause of anemia in this population and that the frequent lack of reticulocytosis, despite bone marrow erythroid hyperplasia, may lead to the underdiagnosis of AIHA in HIV-infected patients.

Authors
Telen, MJ; Roberts, KB; Bartlett, JA
MLA Citation
Telen, MJ, Roberts, KB, and Bartlett, JA. "HIV-associated autoimmune hemolytic anemia: report of a case and review of the literature." J Acquir Immune Defic Syndr 3.10 (1990): 933-937. (Review)
PMID
2204697
Source
pubmed
Published In
Journal of Acquired Immune Deficiency Syndromes
Volume
3
Issue
10
Publish Date
1990
Start Page
933
End Page
937

Zidovudine in asymptomatic human immunodeficiency virus infection: A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter

Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457). After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P<0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001). We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV.

Authors
Volberding, PA; Lagakos, SW; Koch, MA; Pettinelli, C; Myers, MW; Booth, DK; Jr, HHB; Reichman, RC; Bartlett, JA; Hirsch, MS; Murphy, RL; Hardy, WD; Soeiro, R; Fischl, MA; Bartlett, JG; Merigan, TC; Hyslop, NE; Richman, DD; Valentine, FT; Corey, L
MLA Citation
Volberding, PA, Lagakos, SW, Koch, MA, Pettinelli, C, Myers, MW, Booth, DK, Jr, HHB, Reichman, RC, Bartlett, JA, Hirsch, MS, Murphy, RL, Hardy, WD, Soeiro, R, Fischl, MA, Bartlett, JG, Merigan, TC, Hyslop, NE, Richman, DD, Valentine, FT, and Corey, L. "Zidovudine in asymptomatic human immunodeficiency virus infection: A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter." New England Journal of Medicine 322.14 (1990): 941-949.
PMID
1969115
Source
scival
Published In
The New England journal of medicine
Volume
322
Issue
14
Publish Date
1990
Start Page
941
End Page
949

Bioequivalence assessment of zidovudine (Retrovir) syrup, solution, and capsule formulations in patients infected with human immunodeficiency virus.

The objectives of this open-labeled, multiple-dose, three-way-crossover trial were to evaluate the safety and tolerance of zidovudine (Retrovir) oral syrup and to assess the bioequivalence of this formulation relative to zidovudine solution and capsule formulations in human immunodeficiency virus-infected patients. Over the 7-day study, 12 adult male subjects received 12 administrations each of the capsule, solution, and syrup formulations every 4 h (six times daily) in a randomized sequence. Frequent blood samples were collected over the 4-h period after dose 12 was administered. Zidovudine concentrations in plasma were determined by a specific and sensitive radioimmunoassay. Results from statistical analyses indicated that all three formulations were bioequivalent with respect to systemic availability (area under the time-concentration curve) and that the syrup was also equivalent to the solution with respect to the maximum peak concentration in serum. The lower relative maximum peak concentration in serum (approximately 81%) and small delays in time to peak concentration (less than 30 min) of the capsule formulation as compared with the liquid formulations are thought to be due to the additional processes of disintegration and dissolution associated with capsule administration. All three preparations were well tolerated during the 7-day study.

Authors
Drew, RH; Weller, S; Gallis, HA; Walmer, KA; Bartlett, JA; Blum, MR
MLA Citation
Drew, RH, Weller, S, Gallis, HA, Walmer, KA, Bartlett, JA, and Blum, MR. "Bioequivalence assessment of zidovudine (Retrovir) syrup, solution, and capsule formulations in patients infected with human immunodeficiency virus." Antimicrob Agents Chemother 33.10 (October 1989): 1801-1803.
PMID
2589846
Source
pubmed
Published In
Antimicrobial agents and chemotherapy
Volume
33
Issue
10
Publish Date
1989
Start Page
1801
End Page
1803

Zidovudine-induced neutropenia: are we too cautious?

30 patients with recurrent zidovudine-induced neutropenia were followed up for a total of 493 months of treatment to evaluate their risk of bacterial infection. Zidovudine was temporarily discontinued only when the polymorphonuclear (PMN) cell count fell to less than 500/microliters. The incidence of bacterial infection during periods of severe neutropenia (PMN less than 500/microliters) was 230% higher than when the PMN count was 500-1000/microliters, and 600% higher than when the count was greater than 1000/microliters. The difference between periods when the PMU count was 500-1000/microliters and non-neutropenic periods was not significant. The findings suggest that zidovudine therapy can be continued despite neutropenia without a major increase in the incidence of bacterial infection provided the PMN count does not fall to less than 500/microliters.

Authors
Shaunak, S; Bartlett, JA
MLA Citation
Shaunak, S, and Bartlett, JA. "Zidovudine-induced neutropenia: are we too cautious?." Lancet 2.8654 (July 8, 1989): 91-92.
PMID
2567882
Source
pubmed
Published In
The Lancet
Volume
2
Issue
8654
Publish Date
1989
Start Page
91
End Page
92

The sequences of reovirus serotype 3 genome segments M1 and M3 encoding the minor protein mu 2 and the major nonstructural protein mu NS, respectively.

The sequences of the M1 and M3 genome segments of reovirus serotype 3 strain Dearing, which encode protein mu 2, a minor capsid, component, and protein mu NS, one of the two nonstructural proteins, are reported. They are 2304 and 2235 base pairs long, respectively, and proteins mu 2 and mu NS comprise 736 and 719 amino acids, respectively. This completes the sequencing of the reovirus serotype 3 genome: it comprises 23,549 basepairs. Neither protein mu 2 nor protein mu NS possesses any sequence similarity to any protein sequence in gene banks, nor any of the commonly recognized motifs indicative of specialized function. Protein mu 2 has a higher alpha-helix content (36%) than other capsid proteins; for it, the ratio of amino acids in alpha-helix/beta-sheet configuration is 1.2, whereas that of typical reovirus capsid proteins ranges from 0.5 to 0.9. Thus it is not a typical capsid protein. Protein mu NS has a very high alpha-helix content (about 50%; alpha-helix/beta-sheet ratio 2.5), which is very similar to that of the other nonstructural reovirus protein, protein sigma NS. The C-terminal regions of mu NS and various myosins exhibit periodic sequence similarity elements indicative of helical structure. Protein mu NS exists in two forms in infected cells: protein mu NS and a protein, mu NSC, which lacks a region of about 5 kDa at its N-terminus. Pulse-chase analysis in vivo suggests that protein mu NSC is not a cleavage product of protein mu NS; further, protein mu NSC is formed along with protein mu NS in in vitro protein synthesizing systems, whereas protein mu 1C, the cleavage product of protein mu 1, is not. It is likely, therefore, that protein mu NSC is a primary translation product, formed either by ribosomes reading through the first initiation codon of m1 messenger RNA at position 14 and initiating at codon 42, or by de novo internal initiation at this codon.

Authors
Wiener, JR; Bartlett, JA; Joklik, WK
MLA Citation
Wiener, JR, Bartlett, JA, and Joklik, WK. "The sequences of reovirus serotype 3 genome segments M1 and M3 encoding the minor protein mu 2 and the major nonstructural protein mu NS, respectively." Virology 169.2 (April 1989): 293-304.
PMID
2523177
Source
pubmed
Published In
Virology
Volume
169
Issue
2
Publish Date
1989
Start Page
293
End Page
304

The antiretroviral effects of lymphokine-activated killer cells

Authors
Tyler, DS; Stanley, SD; Bumpas, EA; Bartlett, JA; Bolognesi, DP; Weinhold, KJ
MLA Citation
Tyler, DS, Stanley, SD, Bumpas, EA, Bartlett, JA, Bolognesi, DP, and Weinhold, KJ. "The antiretroviral effects of lymphokine-activated killer cells." 1989.
Source
scival
Published In
Surgical Forum
Volume
40
Publish Date
1989
Start Page
435
End Page
437

HIV Therapeutics: An Emerging Science

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "HIV Therapeutics: An Emerging Science." JAMA: The Journal of the American Medical Association 260.20 (November 25, 1988): 3051-3052.
Source
scopus
Published In
JAMA : the journal of the American Medical Association
Volume
260
Issue
20
Publish Date
1988
Start Page
3051
End Page
3052
DOI
10.1001/jama.1988.03410200107036

The sequence of the reovirus serotype 3 L3 genome segment which encodes the major core protein lambda 1.

We present the sequence of reovirus serotype 3 (strain Dearing) genome segment L3 which encodes protein lambda 1, one of the two major components of the core shell. The genome segment is 3896 nucleotides long, with 5'- and 3'-noncoding regions of 13 and 181 nucleotides, respectively. Protein lambda 1 is 1233 amino acids long. It is a slightly acidic protein, with a predicted alpha-helix and beta-sheet content of 23.6 and 28.3%, respectively. Its rather low predicted alpha-helix contact is consistent with its being a structural protein. The 123 amino acid long region at its amino terminus is very hydrophilic and contains three alpha-helical regions, one being 26 amino acids long. Protein lambda 1 contains two functional motifs. The first is a nucleotide binding site -TKGKSSG- starting at residue 8, the other is a "zinc finger" motif centered around amino acid residue 194. This suggests that protein lambda 1 functions during the transcription of either dsRNA into plus strands or of plus strands into minus strands, or during both. It displays no significant sequence similarity to any protein sequence in the GenBank data base.

Authors
Bartlett, JA; Joklik, WK
MLA Citation
Bartlett, JA, and Joklik, WK. "The sequence of the reovirus serotype 3 L3 genome segment which encodes the major core protein lambda 1." Virology 167.1 (November 1988): 31-37.
PMID
3267236
Source
pubmed
Published In
Virology
Volume
167
Issue
1
Publish Date
1988
Start Page
31
End Page
37

HIV therapeutics: an emerging science.

Authors
Bartlett, JA
MLA Citation
Bartlett, JA. "HIV therapeutics: an emerging science." Journal of the American Medical Association 260.20 (1988): 3051-3052.
PMID
3054186
Source
scival
Published In
Journal of the American Medical Association
Volume
260
Issue
20
Publish Date
1988
Start Page
3051
End Page
3052

The sexual behavior of adolescents and risk of AIDS.

Authors
Keller, SE; Schleifer, SJ; Bartlett, JA; Johnson, RL
MLA Citation
Keller, SE, Schleifer, SJ, Bartlett, JA, and Johnson, RL. "The sexual behavior of adolescents and risk of AIDS." Journal of the American Medical Association 260.24 (1988): 3586--.
Source
scival
Published In
Journal of the American Medical Association
Volume
260
Issue
24
Publish Date
1988
Start Page
3586-

Extra-intestinal manifestations of salmonella infections.

While salmonellosis is often considered to affect primarily the gastrointestinal tract, infection at other sites may occur, producing characteristic clinical syndromes. We reviewed cases from our institutions and the literature on focal manifestations of salmonella infections. In the past, most extra-intestinal salmonella infections were caused by S. choleraesuis; however, we found S. typhimurium to be the predominant serotype. The mortality rate for patients in our series was considerably lower than the rate described for focal infections in other reviews. This may in part be due to lower proportion of infections due to S. choleraesuis, improved microbiologic and diagnostic techniques, increased use of ampicillin, and improved surgical techniques. Salmonella endocarditis usually occurs in patients with preexisting heart disease. Unlike other salmonella infections, S. choleraesuis is the most frequent serotype. Salmonella endocarditis is often very destructive, with a fatality rate of 70%. Nonvalvular (mural) endocarditis occurs in one-fourth of patients and survival has not been reported. While antibiotic therapy should be tried initially, if response is not prompt the clinician should look for an associated site of infection (intra- or extra-cardiac abscess), which will often require surgery. Salmonella pericarditis often presents with cardiac or pulmonary symptoms, but typical signs of pericardial disease (pulsus paradoxus, friction rub) or characteristic electrocardiographic changes (low voltage, elevated ST segments) are uncommon. Early diagnosis, before infection involves other areas of the heart, is crucial for survival. In addition to antibiotic therapy, pericardiocentesis or pericardiectomy is required. Salmonella may infect the peripheral or visceral arteries, but the abdominal aorta is the most frequent site of vascular infection. Most patients are men over age 50 with preexisting atherosclerosis of the aorta who do not have a previous history of gastroenteritis. About one-fourth of patients have associated lumbar osteomyelitis. No patients have been reported to survive with medical therapy alone. Specific guidelines for surgical removal of infected aneurysms have been proposed and these (in addition to increased use of ampicillin) may be responsible for higher survival rates in recent years. Due to the high incidence of relapses, postoperative blood cultures should be done routinely. Arterial infection should be considered in any elderly patient with salmonella bacteremia especially with prolonged fever or bacteremia after an "adequate course" of antibiotic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Authors
Cohen, JI; Bartlett, JA; Corey, GR
MLA Citation
Cohen, JI, Bartlett, JA, and Corey, GR. "Extra-intestinal manifestations of salmonella infections." Medicine (Baltimore) 66.5 (September 1987): 349-388.
PMID
3306260
Source
pubmed
Published In
Medicine
Volume
66
Issue
5
Publish Date
1987
Start Page
349
End Page
388
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