The antiviral drug aciclovir does not reduce HIV-1 acquisition in women or men who have sex with men with genital herpes. These are the conclusions of authors of an Article in this week's edition of The Lancet.
Across many observational studies, herpes simplex virus type-2 (HSV-2) infection, the most common cause of genital herpes, is associated with two-fold to three-fold increased risk for HIV-1 infection. Dr Connie Celum, University of Washington, Seattle, USA, and colleagues investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 infection.
The researchers did a randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 positive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants received either aciclovir 400 mg (1637 patients) or placebo (1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling; and every three months for genital examination and HIV testing. The primary outcome was HIV-1 infection and the secondary outcome was incidence of HSV-2 genital ulcers.
A total of 3172 participants (1358 women, 1814 MSM) were included in the analysis (1581 aciclovir, 1591 control). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group and 3.3 per 100 person-years in the placebo group -- thus the HIV incidence rates were not significantly different in the two groups. Incidence of genital ulcers was reduced by 47% in the aciclovir group, and incidence of genital ulcers confirmed to be due to HSV-2 was reduced by 63% in the aciclovir group. No serious adverse events were recorded in relation to aciclovir.
The authors conclude: "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." They add that additional studies will be needed to determine whether the lack of efficacy of aciclovir in reducing HIV acquisition and less than expected efficacy in reducing genital ulcers is due to drug absorption and metabolism, clinical response of genital ulcers to aciclovir, or persistent genital immune response after HSV-2 reactivation.
In an accompanying Comment, Professor Ronald Gray and Professor Maria Weaver, Johns Hopkins University, Baltimore, MD, USA, say that along with other evidence the study shows it is questionable as to whether control of sexually transmitted infections should be promoted specifically for HIV prevention in HIV-negative populations. They conclude: "Thomas Henry Huxley commented that 'The great tragedy of science â€" the slaying of a beautiful hypothesis by an ugly fact.' It is time to reassess the hypothesis and to adjust prevention policy accordingly."
Dr Connie Celum, University of Washington, Seattle, USA T) +1 206 520-3825 E) ccelum@u.washington.edu
Professor Ronald Gray and Professor Maria Weaver, Johns Hopkins University, Baltimore, MD, US T) +1 410 382 7581 / +1 410 955 7818 E) rgray@jhsph.edu
http://multimedia.thelancet.com/pdf/press/aciclovir.pdf
Journal
The Lancet