Tenofovir-Based HIV PrEP Decreases HSV-2 Acquisition



In a placebo-controlled trial conducted in Africa, daily use of pre-exposure prophylaxis regimens containing tenofovir was associated with a modest decrease in herpes simplex virus type 2 seroconversions.


Both herpes simplex virus type 2 (HSV-2) and HIV are transmitted sexually, and HSV-2 infection potentiates acquisition of HIV.

In four randomized, placebo-controlled trials conducted in high-risk populations, daily oral pre-exposure prophylaxis (PrEP) with tenofovir alone or in combination with emtricitabine (FTC) has been shown to decrease HIV acquisition in HIV-uninfected sexual partners of HIV-infected individuals. In a secondary analysis within one such trial, researchers investigated whether tenofovir, which has some anti–HSV-2 activity in vitro and as a vaginal gel in vivo, might have a salutary effect on HSV-2 acquisition when given orally to seronegative partners of seropositive participants.

Between July 2008 and November 2010, 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda were enrolled, and the HIV-uninfected partners were randomized to receive placebo, tenofovir, or FTC-tenofovir. After July 2010, when the efficacy of tenofovir vaginal gel against HSV-2 was demonstrated, the secondary endpoint of HSV-2 protection was added to the study. Of the 1498 participants who were HSV-2–seronegative at baseline and had a final study visit sample available for testing, 131 (78% of whom were men) seroconverted to HSV-2 positivity. Incidence was 5.6/100 person-years in the active PrEP groups and 7.7/100 person-years in the placebo group. The FTC-tenofovir group had slightly fewer seroconversions than the tenofovir-alone group (5.1 vs. 6.1/100 person-years).


The anti–HSV-2 activity of tenofovir-containing PrEP regimens seems to have produced an unanticipated benefit in this study. The effect — albeit small — is important, particularly because HSV-2 infection increases the likelihood of HIV acquisition.