Effect of HSV-2 treatment on HIV-1 genital shedding and plasma viral load

Previous epidemiological data have suggested that herpes simplex virus 2 (HSV-2) infection can increase HIV-1 genital shedding, and in turn increase HIV-1 transmissibility among coinfected people. To date this causal relationship has never been demonstrated.

In an oral late breaker Nicolas Nagot presented findings from a proof of concept, randomised controlled trial of valacyclovir treatment (1000 mg daily vs. placebo for 3 months) among HIV-1/HSV-2 co-infected women not eligible for HAART in Burkina Faso.

The investigators evaluated the effect on HIV-1 genital shedding, HSV-2 genital shedding and HIV-1 plasma viral load. Study participants were followed bi-weekly for 3 months before and 3 months after randomisation for a total of 12 visits.

A cervicovaginal lavage enriched by cervical swabbing was collected for HSV-2 DNA and HIV-1 RNA quantitation by real time PCR. Women who became pregnant during the trial (n=11) were censored in an intent to treat analyses censored. For each woman, the mean quantity of shedding (log copies/mL) between the treatment and the baseline phases were compared. The mean of these differences was then compared between the two trial arms.

140 women (70 in each arm) were randomised to receive valacyclovir or placebo. Mean CD4 counts were 519 and 482 cells/mm³ in the valacyclovir and placebo arms respectively.

The investigators reported good attendance and adherence (93% of visits were attended and a mean adherence rate of 97%). They found the reduction in HIV-1 RNA genital shedding was significantly greater in the valacyclovir arm vs. placebo group in which HIV-1 RNA showed a slight increase (0.26 vs. +0.09 log copies/mL, p= 0.003).

HIV-1 shedding was significantly less persistent in the valacyclovir arm (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).

They also reported a reduction in HIV-1 plasma viral load in the valacyclovir arm ( 0.39 vs. +0.12 log copies/mL, p <0.001) and HSV-2 DNA shedding (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 valacyclovir arm and 54.3% in the placebo arm (p <0.001).

Dr Nagot concluded that although this study was a proof of concept and had no direct public health implications, sustained HSV-2 control could: decrease genital transmissibility; have individual benefits on viral load or immunity and decrease HSW-1 transmission. But at this stage the clinical implications are unclear.

Effect of HSV-2 suppressive therapy on HIV-1 genital shedding and plasma viral load: A proof of concept randomised double-blind placebo controlled trial (ANRS 1285 Trial). Nagot N, Ouedraogo A, Mayaud P et al. 13th CROI, Denver, 2006. Abstract 33LB.