Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.

BACKGROUND: Most people infected with HIV-1 are dually infected with herpes simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it delays HIV-1 disease progression is unknown. We investigated the effect of acyclovir on HIV-1 progression. METHODS: In a trial with 14 sites in southern Africa and east Africa, 3381 heterosexual people who were dually infected with herpes simplex virus type 2 and HIV-1 were randomly assigned in a 1:1 ratio to acyclovir 400 mg orally twice daily or placebo, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per mL or higher and were not taking antiretroviral therapy. We used block randomisation, and patients and investigators were masked to treatment allocation. Effect of acyclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per microL, antiretroviral therapy initiation, or non-trauma related death. As an exploratory analysis, we assessed the endpoint of CD4 falling to <350 cells per microL. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00194519. FINDINGS: At enrollment, the median CD4 cell count was 462 cells per microL and median HIV-1 plasma RNA was 4.1 log(10) copies per microL. Acyclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned acyclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio [HR] 0.84, 95% CI 0.71-0.98, p=0.03). In those with CD4 counts >or=350 cells per microL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per microL by 19% (0.81, 0.71-0.93, p=0.002) INTERPRETATION: The role of suppression of herpes simplex virus type 2 in reduction of HIV-1 disease progression before initiation of antiretroviral therapy warrants consideration. FUNDING: Bill & Melinda Gates Foundation.

Local residents trained as 'influence agents' most effective in persuading African couples on HIV counseling and testing.

Couples in sub-Saharan Africa are the largest group in the world at risk for HIV infection. Couples counseling and testing programs have been shown to reduce HIV transmission, but such programs remain rare in Africa. Before couples counseling and testing can become the norm, it is essential to increase demand for the services. We evaluated the effectiveness of several promotional strategies during a two-year program in Kitwe and Ndola, Zambia. The program attracted more than 7,600 couples through the use of radio broadcasts, billboards, and other strategies. The most effective recruiting technique was the use of local residents trained as "influence agents" to reach out to friends, neighbors, and others in their sphere of influence.

Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.

BACKGROUND: The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort. METHODS: HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed. RESULTS: Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (<5%), except for Trichomonas vaginalis in 14% of HIV-1 infected women. Median baseline CD4 count for HIV-1 infected participants was 462cells/mcL and median HIV-1 plasma RNA was 4.2 log(10) copies/mL. After adjusting for age and African region, correlates of HIV-1 RNA level included male gender (+0.24 log(10) copies/mL; p<0.001) and CD4 count (-0.25 and -0.55 log(10) copies/mL for CD4 350-499 and >500 relative to <350, respectively, p<0.001). CONCLUSIONS: The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00194519.

Evolution of couples' voluntary counseling and testing for HIV in Lusaka, Zambia.

BACKGROUND: : We describe promotional strategies for couples' voluntary HIV counseling and testing (CVCT) and demographic risk factors for couples in Lusaka, Zambia, where an estimated two thirds of new infections occur in cohabiting couples. PRINCIPAL FINDINGS: : CVCT attendance as a function of promotional strategies is described over a 6-year period. Cross-sectional analyses of risk factors associated with HIV in men, women, and couples are presented. Community workers (CWs) recruited from couples seeking CVCT promoted testing in their communities. Attendance dropped when CW outreach ended, despite continued mass media advertisements. In Lusaka, 51% of 8500 cohabiting couples who sought HIV testing were concordant negative for HIV (MF) and 26% concordant positive (MF); 23% had 1 HIV-positive partner and one HIV-negative partner, with 11% HIV-positive man/HIV-negative woman (MF) and 12% HIV-negative man/HIV-positive woman (FM). HIV infection was associated with men's age 30 to 39, women's age 25 to 34, duration of union <3 years, and number of children <2. Even among couples with either 1 or 2 or no risk factors, HIV prevalence was 45% and 29%, respectively. CONCLUSIONS: : Many married African adults do not have high-risk profiles, nor realize that only 1 may be HIV positive. Active and sustained promotion is needed to encourage all couples to be jointly tested and counseled.

Regional differences in prevalence of HIV-1 discordance in Africa and enrollment of HIV-1 discordant couples into an HIV-1 prevention trial.

BACKGROUND: Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported. METHODOLOGY/PRINCIPAL FINDINGS: The Partners in Prevention HSV-2/HIV-1 Transmission Trial ("Partners HSV-2 Study"), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrollment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counseling and testing, and to correlate with enrollment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8-31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrollment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counseling and testing rates and access to palliative care/basic health care (r = 0.74, p = 0.09). CONCLUSIONS/SIGNIFICANCE: HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials.