Control of herpes simplex with daily treatment or with a vaccine should be considered as a strategy to reduce HIV transmission, urge researchers who carried out a large randomised study of the effects of an anti-herpes drug on HIV in African women. Their findings are published in the February 22nd edition of the New England Journal of Medicine.
The ANRS 1285a study, funded by the French Agence Nationale de Recherches sur le Sida (ANRS) and the United Kingdom’s Department for International Development, was first presented at the 2006 Conference on Retroviruses and Opportunistic Infections in Denver (click here for full results).
The study showed that HIV-positive women randomised to receive daily treatment with valaciclovir, an anti-HSV2 drug, had lower amounts of HIV in their genital fluids and in their blood. These women were not receiving antiretroviral treatment.
The reduction in plasma viral load at the end of the three month study was 0.5 log10, a decline associated with a reduction in the risk of disease progression, notes Dr Lawrence Corey of the University of Washington, Seattle, in an editorial accompanying the study report.
The authors point out that the degree of viral load suppression increased with time on treatment, suggesting that a longer duration of treatment with valaciclovir might lead to a greater reduction in viral load. Longer studies are needed, they say, to examine the impact both on HIV disease and HIV transmission.
Valaciclovir appears to exert its effect on HIV viremia not through direct mechanisms, but by reducing HSV-2 levels. The authors speculate that reducing HSV-2 levels may reduce the activation of cells latently infected with HIV (HSV-2 can activate latent HIV), and discourages clinical episodes of herpes simplex that lead to an upsurge of HIV replication. Replication of HSV-2 without symptoms may have the same effect.
Dr Philippe Mayaud, one of the researchers from the London School of Hygiene and Tropical Medicine who carried out the study, said: “Our results have important potential implications for public health and clinical practice, as HSV-2 control could become a new form of HIV prevention targeting HIV-infected individuals, as well as providing clinical benefits.”
“Importantly, an HSV vaccine that would either prevent HSV infection or diminish the clinical and sub-clinical manifestations of HSV with a similar efficacy on HIV as HSV suppressive therapy, would represent a long-lasting form of HIV prevention. The development and evaluation of an HSV vaccine should rank high on the international research agenda.”
Nagot N et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med 356 (8): 790-99, 2007.
Corey L. Synergistic copathogens – HIV-1 and HSV-2. N Engl J Med 356 (8): 854-856, 2007.