16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

HERPES SIMPLEX VIRUS TYPE 2 (HSV-2) SUPPRESSIVE THERAPY TO REDUCE GENITAL AND PLASMA HIV-1 RNA: OVERVIEW OF ANRS 1285 TRIALS, POTENTIAL MECHANISMS AND FUTURE INTERVENTIONS

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. TuAc0501

P. Mayaud¹, A. Ouedraogo², N. Nagot¹, I. Konate², L. Vergne², H. Weiss¹, A. Sanon², P. Van de Perre³, ANRS1285 Study Group
¹ London School of Hygiene and Tropical Medicine, Infectious and Tropical Diseases, London, United Kingdom, ² Centre Muraz, STI/HIV/AIDS, Bobo Dioulasso, Burkina Faso, ³ CHU Montpellier, Laboratoire de Bacterio-Virologie, Montpellier, France

BACKGROUND: There is strong biological and epidemiological evidence linking HSV-2 to HIV transmission, but absence of rigorous intervention data to prove this hypothesis.

METHODS: We conducted two proof-of-concept randomised placebo-controlled trials measuring the impact of valacyclovir (1g-daily for 3-months) on plasma and genital HIV-1 RNA among HSV/HIV-infected women taking HAART (ANRS 1285b), or not needing HAART (ANRS 1285a), in Burkina Faso. We discuss results of both trials, which have been reported separately, and mechanisms underlying the findings.

RESULTS: The ANRS 1285a trial (N=140) showed that both the frequency and quantity of genital HIV-1 RNA shedding were significantly reduced by valacyclovir, with a 20% decrease in quantity of HIV-1 RNA from one bi-weekly measurement to the next (p<0.01). There was a rapid and sustained significant reduction in plasma HIV-1 RNA of 0.5 log copies/mL over 3-months. The ANRS 1285b (N=60) did not show impact of valacyclovir on genital HIV-1 RNA overall, but found a borderline-significant effect on genital HIV-1 quantity in the subgroup of women shedding HIV-1 at baseline (p=0.09). There was some evidence of a reduction in plasma HIV-1 RNA (p=0.06). Results of both trials suggest that effect on genital HIV-1 RNA is driven partly by concomittant 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.

CONCLUSIONS: The ANRS1285 trials are the first to demonstrate impact of HSV on HIV transmissibility in vivo. If confirmed by ongoing intervention trials, these findings support an important role of HSV-2 control in HIV prevention. Additionally, our data provide rationale for interventions evaluating the impact of (val)acyclovir on HIV immunological and virological correlates.

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2006-08-13
TuAc0501

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