Effect of herpes simplex therapy on genital and plasma HIV viral load
Polly Clayden, HIV i-Base
There is strong evidence associating infection with herpes simplex virus type 2 (HSV-2) with HIV transmission. More than 80% of people with HIV are co-infected with HIV-2 in Africa.
In an oral presentation, Phillippe Mayaud reported findings from the ANRS 1285 trials. These are two proof-of-concept, randomised, placebo-controlled trials measuring the impact of valacyclovir on plasma and genital viral load among HSV/HIV-infected women either receiving HAART (ANRS 1285b), or not needing HAART (ANRS 1285a), in Burkina Faso. [1, 2]
In ANRS 1285a, 140 women were randomised to receive valacyclovir (Ig daily) or placebo. Plasma and genital viral load were measured twice-weekly and data were available for analysis from 136 women. The investigators reported a -0.41 and -0.58 log10 copies/mL reduction in quantity of genital and plasma HIV-I RNA respectively over three months, in the women receiving valacyclovir. They also found a 65% reduction in HSV-2 genital shedding and an 84% reduction of occurrence of ulcers.
In ANRS 1285b, 60 women receiving HAART were randomised to valacyclovir or placebo (mean CD4 count: 266 and 295 cells/mm3 respectively).
The investigators reported that in this trial there was some evidence of a reduction in plasma HIV-1 RNA among the women on valacyclovir, but it did not reach statistical significance (p=0.06). They found very little HSV-2 shedding but a further reduction of 70% in the valacyclovir arm, and no occurrence of ulcers in both arms.
They explained that this was the First randomized clinical trial to demonstrate casual relationship between HSV-2 and HIV-1 replication and that the effect persists amongst the small subset of women on HAART who are baseline shedders.
They wrote Results of both trials suggest that effect on genital HIV-1 RNA is driven partly by concomitant reduction in plasma HIV-1 RNA, and partly by the facilitating role of HSV-2 on HIV-1 genital replication, although this effect was limited in women taking HAART. Plausible explanations for impact on plasma HIV-1 include immunological mechanisms, circulating soluble factors and/or HIV-infected cells, or effect on other herpes-related viruses.
Dr Mayaud questioned whether these findings would have sufficient impact to reduce HIV transmission, and suggested that we await the results of ongoing trials among serodiscordant couples from Celum et al. He also explained that specific trials were needed to determine whether virological impact at systemic level be translated into impact on CD4.
- Mayaud P, Ouedraogo A, Nagot N et al. Herpes simplex virus type 2 (HSV-suppressive therapy to reduce genital and plasma HIV-1 RNA: overview of ANRS 1285 trials, potential mechanisms and future interventions. XVI International AIDS Conference, August 2006, Toronto. Oral abstract TUAC0501.
- Nagot N, Ouedraogo A, Konate I et al. Impact of valacyclovir on genital and plasma HIV-1 RNA: a randomised controlled trial among women taking HAART (ANRS 1285b). XVI International AIDS Conference August 2006, Toronto. Poster abstract TUPE0402.