13th Conference on Retroviruses and Opportunistic Infections Denver, Colorado - February 5-8, 2006

Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 33LB

Nicolas Nagot^1,2, A Ouedraogo², P Mayaud¹, I Konate², L Vergne², H Weiss¹, V Foulongne³, D Djagbare², M Segongy³, P Vande Perre³, and ANRS 1285 Study Group
¹London Sch of Hygiene and Tropical Med, UK; ²Ctr Muraz, Bobo-Dioulasso, Burkina Faso; and ³Univ Hosp, Montpellier, France

BACKGROUND: Epidemiological data suggest that HSV-2 infection can increase HIV-1 genital shedding, thus potentially increasing HIV-1 transmissibility from co-infected individuals. Although biologically plausible, this causal relationship has never been proven.

METHODS: We conducted a proof-of-concept, randomized controlled trial of Valacyclovir (VACV) suppressive treatment (1.0 g daily for 3 months) among HIV-1/HSV-2 co-infected women not eligible for HAART in Burkina Faso. We evaluated effect on HIV-1 genital shedding (primary outcome), as well as HSV-2 genital shedding and HIV-1 plasma viral load (secondary outcomes). Participants were followed bi-weekly for 3 months prior to, and 3 months after randomization for a total of 12 visits. At each visit, a cervicovaginal lavage enriched by cervical swabbing (eCVL) was collected for HSV-2 DNA and HIV-1 RNA quantitation by real time PCR. Primary statistical analyses were based on an intention-to-treat approach, censoring women who became pregnant during the trial. For each woman, the outcome was the difference in mean quantity of shedding (log copies/mL) between the treatment and the baseline phases. The mean of these differences (Δ) was then compared between the 2 arms. The effect of the intervention on frequency and persistence of viral shedding was estimated using logistic regression.

RESULTS: We randomized 140 women (70 in each arm) to VACV or placebo (mean CD4 count 519 and 482/µL, respectively). Overall, 93% of visits were attended, with a mean treatment compliance of 97%. The reduction in HIV-1 RNA genital shedding was significantly greater in the VACV group than in the placebo group (Δ= –0.26 vs +0.09 log copies/mL, p = 0.003). HIV-1 shedding was significantly less persistent in the VACV group (14.3% vs 27.1% shed at each visit; 27.1% vs 44.3% shed at ≥50% of visits; 32.9% vs 14.3% shed at <50% of visits; and 25.7% vs 14.3% never shed, p = 0.007). HIV-1 PVL was also reduced in the VACV group (Δ= – 0.39 vs +0.12 log copies/mL, p <0.001), as was HSV-2 DNA shedding (Δ = –0.22 vs +0.18 log copies/mL, p <0.001). The proportion of women shedding HSV-2 at least once was 18.6% in the VACV arm and 54.3% in the placebo arm (p <0.001).

CONCLUSIONS: Active HSV-2 infection is causally related to increased HIV-1 genital shedding, with implications at the systemic level. HSV-2 control interventions may contribute to reduce sexual transmissibility of HIV-1 and may delay HAART eligibility in dually infected women.

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2006-02-05
33LB

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