William Lang

The San Francisco Men's Health Study: III. Reduction in human immunodeficiency virus transmission among homosexual/bisexual men, 1982-86.

The prevalence and incidence of infection by the human immunodeficiency virus (HIV) has been under study in a cohort of 1,034 single men recruited by area probability sampling from a six kilometer square area of San Francisco where the epidemic of acquired immunodeficiency syndrome (AIDS) has been most severe. Prevalence of infection among homosexual/bisexual study subjects increased from an estimated 22.8 per cent during the last half of 1982 to 48.6 per cent during the period July through December 1984. During three subsequent six-month periods, prevalence remained stable at approximately 50 per cent. Annual infection rates, measured by seroconversion among seronegative study subjects, decreased from an estimated 18.4 per cent per year from 1982 to 1984, to 5.4 and 3.1 per cent during the first and second halves of 1985, and to 4.2 per cent during the first six months of 1986. These declines were associated with reductions of 60 per cent or more in the prevalence of high-risk sexual practices associated with both acquiring and disseminating infection by the human immunodeficiency virus.

An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease.

Dehydroepiandrosterone (DHEA) is a naturally occurring adrenal steroid reported to have immunomodulatory and antiviral activity in cellular and animal models as well as modest in vitro antiretroviral activity against human immunodeficiency virus (HIV). A phase I dose-escalation study was performed to evaluate the safety and pharmacokinetics of DHEA in subjects with symptomatic HIV disease and an absolute CD4 lymphocyte count between 250 and 600 cells/microliters. Thirty-one subjects were evaluated and monitored for safety and tolerance. The oral drug was administered three times daily in doses ranging from 750 mg/day to 2,250 mg/day for 16 weeks. Some immunological and virological parameters were monitored as well. The drug was well tolerated and no dose-limiting side effects were noted. Dose proportionality was evidenced neither by the serum DHEA nor by DHEA-S time-concentration curves for the three dosing groups. However, the study cohort appeared to consist of two subpopulations with markedly different bioavailability for a given DHEA dose. No sustained improvements in CD4 counts nor decreases in serum p24 antigen or beta-2 microglobulin levels were observed. However, serum neopterin levels decreased transiently by 23-40% at week 8 compared with baseline in all dosing groups. DHEA was well tolerated by patients with mild symptomatic HIV disease; evaluation of this agent for efficacy in HIV disease would require randomized, controlled trials.

A phase Ii safety and efficacy study of amprenavir in combination with zidovudine and lamivudine in Hiv-infected patients with limited antiretroviral experience

OBJECTIVE To determine the safety and efficacy of amprenavir (APV) in combination with lamivudine (3TC) and zidovudine (ZDV). DESIGN Multicenter, randomized, partially blinded trial. SETTING Nine study sites in the United States and Europe. PATIENTS A group of 84 HIV-infected subjects with no prior 3TC or protease inhibitor therapy experience, CD4 cell count > or = 150 x 10(6) cells/l, and plasma HIV RNA > 10000 copies/ml. INTERVENTIONS 3TC/ZDV with one of three doses of APV (900, 1050, or 1200 mg) versus 3TC/ZDV with 1050 mg placebo. All medications were dosed twice daily. The 1050 mg placebo and the APV 1050 mg dose were administered blinded. After 12 weeks, APV 1050 mg was substituted for 1050 mg placebo in the control group and the blind was maintained. MAIN OUTCOME MEASURES Reduction in plasma HIV RNA from baseline; proportion of subjects with plasma HIV RNA < 400 copies/ml; and an increase in CD4 cell count from baseline. RESULTS During the initial 12-week study period, APV/3TC/ZDV-treated subjects had greater viral suppression than the group receiving two nucleosides. By 48 weeks, 89% of subjects in the group taking the highest APV dose (1200 mg) had plasma HIV RNA < 400 copies/ml while 42% of the 900 mg group and 60% of the 3TC/ZDV group (1050 mg APV added at week 12) had plasma HIV RNA < 400 copies/ml using an as-treated analysis. By 60 weeks, 86% of subjects in the APV 1200 mg group had plasma HIV RNA < 400 copies/ml in the as-treated analysis, while 25% (900 mg), 43% (1050 mg), and 20% (1200 mg) of subjects had viral load <400 copies/ml in a strict intent-to-treat analysis owing to treatment discontinuations. Median CD4 cell count increases at week 60 were highest for the three treatment groups who received APV throughout the study, by intent-to-treat and as-treated analyses. The most common adverse events considered to be possibly drug related were nausea, rash, oral paresthesia, diarrhea, and fatigue. CONCLUSIONS Treatment with APV, dosed at 1200 mg twice daily in combination with 3TC/ZDV, resulted in sustained viral suppression. This combination represents a potent alternative initial antiretroviral regimen for protease inhibitor-naive individuals.

Cd8+ T lymphocytes and progression to Aids in Hiv-infected men: some observations

The relationship between CD8+ lymphocyte counts and progression to AIDS was studied in 340 HIV-1-seropositive men participating in a population-based prospective study. Overall, the relative hazard for developing AIDS during 60 months of observation was slightly elevated (1.08, P = 0.003), indicating an 8% increase in risk of progression for every 100 CD8+ cell count increment. When the data were analyzed in relation to date of diagnosis, the relative hazard was depressed (0.90, P less than 0.001) for the period 6 months prior to diagnosis, but was close to 1.0 for the period 6-36 months prior to diagnosis. These findings suggest a complex relationship between CD8+ cell counts and progression to AIDS, with the possibility that various subsets of the CD8+ compartment play different roles.

Intravascular and pleural involvement by Pneumocystis carinii in a patient with the acquired immunodeficiency syndrome (AIDS)

Excerpt To the Editor:WhereasPneumocystis cariniipneumonia is common in patients with human immunodeficiency virus (HIV) infection, pleural and extrapulmonary infection have been thought to be rare...

A phase II trial of dual protease inhibitor therapy: Amprenavir in combination with indinavir, nelfinavir, or saquinavir

This study evaluated dual protease inhibitor (PI) regimens containing amprenavir (APV) in PI-naive, HIV-1-infected patients over 48 weeks. Patients were randomized to 800-mg APV combined with 800-mg indinavir (IDV), 750-mg nelfinavir (NFV), or 800-mg saquinavir-soft gel capsule (SGV-SGC), all three times daily without nucleoside reverse transcriptase inhibitors, or APV given alone for 3 weeks and then with 150-mg lamivudine (3TC) and 300-mg zidovudine (ZDV), twice daily. Dual PI therapy demonstrated substantial antiviral activity and was generally safe and well tolerated. Eight patients had virologic failure; 5 were receiving dual PI therapy and 3 were in the APV/3TC/ZDV arm. The protease I50V mutation characteristic of APV resistance was not observed, although other key PI mutations were selected in 4 patients failing therapy, 2 of whom had PI resistance at baseline.