Aciclovir, an antiviral drug, does not reduce the transmission of HIV-1 in women or men who have genital herpes who have sex with men, according to the authors of an Article released on June 20, 2008 in The Lancet.
Herpes simplex virus type-2 (HSV-2) infection, the most common cause of genital herpes, has been associated with a two to three-fold increased risk of HIV-1 infection. To help determine the nature of this association, Dr. Connie Celum, University of Washington, Seattle, USA, and colleagues, examined the effects of HSV-2 suppression with aciclovir on HIV-1. This was done using HIV-negative, HSV-2 positive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA.
In the randomized, placebo-controlled phase III trial, participants were assigned to be administered 400mg of aciclovir (1,637 patients) or a placebo (1,640 patients) for 12-18 months. Followups were performed monthly to examine the dispensation of the study drug, perform adherence counseling, pill count (self reported), and risk reduction counseling. Every three months, genital examinations and HIV tests were performed. The tested outcomes were HIV-1 infection and and HSV-2 genital ulcers.
The participants were 1,358 women and 1,814 MSM included in the analysis: 1,581 in the aciclovir group and 1,591 in the control group. HIV-1 incidence was not significantly different between the groups. That said, the incidence of gentical ulcers was reducted by 47% in the aciclovir group, and 65% of genital ulcers confirmed to be due to HSV-2. There were no serious adverse events to the medication recorded.
In conclusion, the authors state that aciclovir has no impact on the HIV-1 transmission rates in these populations. “Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.” Additionally, they say, that futher studies should be performed to ascertain whether this lack of efficacy is due to drug absorption and metabolism, the clinical response of genital ulcers to the drug, or the persistent genital immune response after HSV-2 is activated.
Professor Ronald Gray and Professor Maria Weaver, Johns Hopkins University, Baltimore, MD, USA, contributed an accompanying comment in which they debate if the control of sexually transmitted infections should be promoted for HIV prevention in HIV negative populations. “Thomas Henry Huxley commented that ‘The great tragedy of science – the slaying of a beautiful hypothesis by an ugly fact.’ It is time to reassess the hypothesis and to adjust prevention policy accordingly.”
Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial
Connie Celum, Anna Wald, James Hughes, Jorge Sanchez, Stewart Reid, Sinead Delany-Moretlwe, Frances Cowan, Martin Casapia, Abner Ortiz, Jonathan Fuchs, Susan Buchbinder, Beryl Koblin, Sheryl Zwerski, Scott Rose, Jing Wang, Lawrence Corey, and the HPTN 039 Protocol Team
Lancet 2008; 371: 2109-19
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Reassessing the hypothesis on STI control for HIV prevention
Ronald H Gray, Maria J Wawer
Lancet 2008; 371: 2065-66
Written by Anna Sophia McKenney