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Previous Volume 358:1560-1571 April 10, 2008 Number 15 Next

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ABSTRACT

Background Infection with herpes simplex virus type 2 (HSV-2) is associated with an increased risk of acquiring infection with the human immunodeficiency virus (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition.

Methods Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2. We enrolled female workers who were HIV-seronegative and HSV-2–seropositive in a randomized, double-blind, placebo-controlled trial of suppressive treatment with acyclovir (400 mg twice daily). Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months, depending on enrollment date. The primary outcome was the incidence of infection with HIV. We used a modified intention-to-treat analysis; data for participants who became pregnant were censored. Adherence to treatment was estimated by a tablet count at each visit.

Results A total of 821 participants were randomly assigned to receive acyclovir (400 participants) or placebo (421 participants); 679 (83%) completed follow-up. Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years, respectively. The incidence of HIV infection was 4.27 per 100 person-years (27 participants in the acyclovir group and 28 in the placebo group), and there was no overall effect of acyclovir on the incidence of HIV (rate ratio for the acyclovir group, 1.08; 95% confidence interval, 0.64 to 1.83). The estimated median adherence was 90%. Genital HSV was detected in a similar proportion of participants in the two study groups at 6, 12, and 24 months. No serious adverse events were attributable to treatment with acyclovir.

Conclusions These data show no evidence that acyclovir (400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection with HIV. (Current Controlled Trials number, ISRCTN35385041 [controlled-trials.com] .)

Source Information

From the London School of Hygiene and Tropical Medicine, London (D.W.-J., H.A.W., K.B., C.T., D.R., D.E., T.C., L.K., I.H., R.H.); the African Medical and Research Foundation (D.W.-J., M.R., K.M.) and the National Institute for Medical Research (J.C., K.B., C.T., D.E., R.B., L.K., I.H.) — both in Mwanza, Tanzania; and the Laboratoire de Microbiologie, Hôpital Saint Louis (J.L.G.), and INSERM Unité 743 and Université Paris V (L.B.) — both in Paris.

This article (10.1056/NEJMoa0800260) was published at www.nejm.org on March 12, 2008.

Address reprint requests to Dr. Watson-Jones at the Department of Infectious and Tropical Diseases, Keppel St., London WC1E 7HT, United Kingdom, or at deborah.watson-jones{at}lshtm.ac.uk.

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