Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: A subgroup analysis of a randomized trial

Connie Celum, Rhoda A. Morrow, Deborah Donnell, Ting Hong, Craig Hendrix, Katherine K. Thomas, Kenneth H. Fife, Edith Nakku-Joloba, Andrew Mujugira, Jared M. Baeten

Research output: Contribution to journalArticle


Background: Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC-TDF) reduces the risk for HIV-1 acquisition. Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2). Objective: To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition. Design: Subgroup analysis of data from a randomized, placebocontrolled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245) Setting: Multiple sites in Kenya and Uganda. Participants: Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1-infected partner. Measurements: HSV-2 seroconversion. Results: A total of 131 participants seroconverted to HSV-2 (79 of 1041 assigned to tenofovir or FTC-TDF PrEP [HSV-2 incidence, 5.6 per 100 person-years] and 52 of 481 assigned to placebo [HSV-2 incidence, 7.7 per 100 person-years]). The hazard ratio (HR) for HSV-2 acquisition with daily oral PrEP was 0.70 (95% CI, 0.49 to 0.99; P = 0.047) compared with placebo, and the absolute risk reduction was 2.1 per 100 person-years. Among the 1044 participants with HSV-2-infected partners, the HR for PrEP was 0.67 (CI, 0.46 to 0.98; P = 0.038) compared with placebo, and the absolute risk reduction was 3.1 per 100 person-years. Limitation: Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available. Conclusion: Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women. Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalAnnals of Internal Medicine
Issue number1
Publication statusPublished - Jul 1 2014


ASJC Scopus subject areas

  • Internal Medicine

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