Preexposure Prophylaxis with Tenofovir or Emtricitabine-Tenofovir Reduces Herpes Simplex Virus Type -2 Transmission

August 1, 2014

This study demonstrates an added benefit to tenofovir-based preexposure prophylaxis regimens in preventing HSV-2.

Pre-exposure prophylaxis with the oral antiretrovirals tenofovir or emtricitabine combined with tenofovir has been shown to reduce the risk of HIV infection significantly in several randomized controlled clinical trials.1

Because of suggested activity against Herpes Simplex Virus type 2(HSV-2) in vitro,2 a recent study was designed to examine the efficacy of daily world pre-exposure prophylaxis regimens with tenofovir or emtricitabine-tenofovir in reducing the acquisition of HSV-2.

As reported in the Annals of Internal Medicine, a secondary analysis from a randomized placebo-controlled trial conducted in 9 research sites in Kenya and Uganda was conducted.3 The investigators examined HSV-2 seroconversion rates in the study population. They identified 131 participants who had incident HSV-2 infections with an incidence of 5.64 per 100 person–years in the pre-exposure prophylaxis group and 7.7 per 100 person–years in the placebo group. Pre-exposure prophylaxis was associated with a hazard ratio for HSV-2 acquisition of .70 (95% confidence interval, 0.49 to 0.99; P =0.047).3

The investigators concluded that pre-exposure prophylaxis with oral tenofovir-based regimens reduced HSV-2 acquisition by 30% compared with placebo in subjects who were initially HSV-2 seronegative.

This study has some limitations including its inability to detect and exclude individuals with acute HSV-2 infection at the beginning of the study due to the unavailability of laboratory methods. Also, the study is a secondary analysis of the clinical trial that was not originally designed to test the efficacy of tenofovir for preventing HSV-2 seroconversion.3Key Point: HSV-2 is highly prevalent in HIV-1-infected patients and is a significant risk factor for HIV-1 acquisition. This study demonstrates an added benefit to tenofovir- based preexposure prophylaxis regimens in preventing HSV-2.


1. Grant RM, Lama JR, Anderson PL, et al, iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010; 363:2587-2599.
2.Balzarini J, Holy A, Jindrich J, et al. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother. 1993; 37:332-338.
3. Celum C, Morrow RA, Donnell D, et al, for the Partners PrEP Study Team. 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. Ann Intern Med. 2014;161:11-19.