Brief report: effectiveness of combination antiretroviral therapy on survival and opportunistic infections in a developing world setting: an observational cohort study.

BACKGROUND: The prolonged effectiveness of antiretroviral therapy (ART) in a developing country is not well established. METHODS: An observational database was established at the HIV clinic of the Almenara Hospital in Lima, Peru in 1996. All 564 initially antiretroviral-naive HIV-infected persons (mean CD4 count of 91 cells/mm3) who received combination ART were followed over time. RESULTS: The overall survival rate was 96% at year 2, 94% at year 4, and 91% at year 5. Among persons who initiated therapy with CD4 counts <100 cells/mm3, the overall survival rate at 3 years was 95%. Opportunistic infections while on ART occurred in 20% of persons. Patients who received 2 reverse transcriptase (RT) inhibitors plus a protease inhibitor had slightly better survival rates and less opportunistic disease in the first year of therapy as compared with those receiving 2 RT inhibitors and a nonnucleoside reverse transcriptase inhibitor or 3 RT inhibitors. CONCLUSIONS: This study demonstrates the long-term effectiveness of ART in a developing country urban setting. It provides evidence of the importance of continuing global financing initiatives to provide widespread HIV therapy for countries in the developing world.

Antiretroviral therapy for HIV-1 vaccine efficacy trial participants who seroconvert.

Instead of preventing infection, most HIV-1 vaccines in clinical trials are directed at inducing cytotoxic HIV-1-specific T cell (CTL) responses which may control viral replication and subsequently modify the clinical course of HIV-1 infection. Thus, vaccine efficacy trial designs must follow participants who become HIV-infected and monitor the course of HIV-1 infection, in order to assess the effect of vaccination on HIV-1 disease progression. This post-infection evaluation will assess time to reach specific CD4 and viral load thresholds as well as time to initiation of antiretroviral therapy. This paper discusses current literature and guidelines on the initiation of highly active antiretroviral therapy (HAART) for persons who become HIV-infected during HIV-1 vaccine trials, focusing both on acute and early HIV-1 infection, since participants in HIV-1 vaccine and other prevention trials will typically be identified within 3-6 months after HIV-1 acquisition. A standardized HAART protocol for HIV-1 vaccine efficacy trial participants who become HIV-infected is essential to the evaluation of CTL-based HIV-1 vaccines on the natural history of HIV-1 infection.

The natural history of untreated HIV infection in Lima, Peru: implications for clinical trial endpoints for HIV vaccines.

Most candidate HIV vaccines are directed at priming memory T cell responses and are being evaluated on their effects on post acquisition viremia and/or disease progression. These vaccines are being studied in areas of high HIV-1 prevalence. As such, we evaluated the frequency of CD4+ T cell decline and time course of opportunistic infections of patients presenting at a major metropolitan hospital in Lima, Peru, an area where such candidate vaccines are being tested. We examined 92 patients with untreated HIV-1 in calendar year 2002: 35% presented with CD4+ T cell counts of <200, 25% between 201 and 400, and 17% with >400 cells/mm3, 30 of 92 patients presented with overt AIDS, 6 were without an AIDS defining OI but CD4 counts <200. Over the course of follow-up, CD4 count decreased by a mean of 31 cells/mm3/year in women and 28 in men (p>0.5). Among persons presenting with CD4 counts >250 cells/mm3, the median time to first OI was 3.5 years. If clinical endpoints are required to evaluate the clinical effectiveness of T cell based vaccines, extended clinical follow-up of subjects enrolled in such trials will be required.

Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men.

OBJECTIVES: To assess safety and acceptability of penile application of BufferGel (ReProtect, Baltimore, MD) and PRO 2000 Gel (Indevus Pharmaceuticals, Lexington, MA)compared with placebo among low-risk sexually abstinent men and HIV-positive sexually abstinent men. DESIGN: Seventy-two healthy low-risk men (36 uncircumcised) and 25 HIV-positive men (12 uncircumcised) were enrolled in 3 double-blind, single-center studies as follows: 36 low-risk men in a study of BufferGel and K-Y Jelly (McNeil-PPC, Skillman, NJ) placebo; 36 low-risk men in a study of PRO 2000 Gel and vehicle placebo; and 25 HIV-positive men in a crossover study of BufferGel, PRO 2000 Gel, and K-Y Jelly placebo. METHODS: Participants applied product to the penis on 7 consecutive nights, kept study diaries, and were then interviewed and examined. Urine was tested for inflammation by leukocyte esterase. RESULTS: No serious adverse events (AEs) or urethral inflammation was detected. During use of BufferGel, 3 low-risk men (13%) reported 6 AEs and 2 HIV-positive men (8%) reported 3 AEs. During use of PRO 2000 Gel, 4 low-risk men (17%) reported 6 AEs and 1 HIV-positive participant (4%) had 1 AE. AE rates during use of BufferGel and PRO 2000 Gel use were not significantly different from rates observed during placebo. One low-risk man (4%) would object to his partners using BufferGel and 3 (13%) to PRO 2000 Gel. Two HIV-positive men (8%) reported they would object to partners using either BufferGel or PRO 2000 Gel. CONCLUSIONS: Daily application of BufferGel and PRO 2000 Gel directly to the penis consecutively for 7 days was generally safe and well tolerated among healthy low-risk men and HIV-positive men. These microbicides have acceptable safety profiles to proceed with planned phase 3 vaginal microbicide trials.

Safety and acceptability of the Reality condom for anal sex among men who have sex with men.

OBJECTIVES: To assess safety and acceptability of Reality condoms for anal sex among men who have sex with men. METHODS: Crossover study among HIV-seroconcordant (33 HIV-negative and 5 HIV-positive) monogamous male couples, randomized to latex male and Reality condom use with anal sex. RESULTS: Slippage with removal was reported more frequently with Reality than male latex condoms [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.2-5.8 for receptive partners and OR, 34.1; 95% CI, 13.8-84.1 for insertive partners]. Receptive partners more frequently reported pain or discomfort (OR, 5.0; 95% CI, 2.6-9.4) and rectal bleeding (OR, 1.9; 95% CI, 0.9-4.1) with Reality condoms than male condoms. Over 20% reported willingness to use the Reality condom in the future with a partner of unknown HIV status; willingness was associated with past problems with male condoms and no problems with Reality condoms among receptive partners, and with past use of Reality condoms and HIV seropositivity among insertive partners. CONCLUSIONS: Men reported more frequent problems with Reality condoms than male latex condoms used for anal intercourse, particularly slippage, discomfort, and rectal bleeding. Design modifications, training, and research on the clinical significance of safety outcomes are needed for use of Reality condoms with anal sex.

Correlates of prevalent and incident Kaposi's sarcoma-associated herpesvirus infection in men who have sex with men.

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is common among men who have sex with men (MSM). To determine correlates of infection, 578 human immunodeficiency virus (HIV)-negative MSM were assessed by serologic assays, questionnaires, and physical examinations. At baseline, 76 (16%) of 474 participants were KSHV seropositive. Prevalent KSHV infection was significantly associated with hepatitis A (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5-7.5), hepatitis B seropositivity (OR, 2.6; 95% CI, 1.4-4.8), herpes simplex virus (HSV)-2 (OR, 2.4; 95% CI, 1.3-4.4), and >4 male partners in the previous 6 months (OR, 1.9; 95% CI, 1.1-3.2). Fifteen KSHV seroconversions (4%) were observed for an incidence of 3.8/100 person-years, similar to HSV-1 incidence in this cohort and more frequent than incidence of HIV and HSV-2. Reporting > or =1 HIV-positive partner (OR, 5.9; 95% CI, 1.8-19.3), amyl nitrite use (OR, 7.0; 95% CI, 2.1-23.0), and lymphadenopathy in the past 6 months (OR, 7.7; 95% CI, 1.9-31.0) correlated with KSHV seroconversion.