1. In this double-blinded randomized controlled study, women randomized to apply intracoital vaginal tenofovir gel were significantly less likely to seroconvert to herpes simplex virus type 2 (HSV-2) compared to women who applied identical-appearing placebo gel.
2. Tenofovir has had mixed results in preventing HIV transmission when used in a topical vaginal gel form, but has shown to reach effective concentrations for treatment of HSV-2.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Around the world, HSV-2 is the most common cause of genital ulcer disease. It has a seroprevalence of 15.7% in persons aged 14 to 49 years in the U.S. and up to 80% of sexually active women in Sub-Saharan Africa. Tenofovir is a nucleotide reverse-transcriptase inhibitor widely used in its oral form for antiretroviral therapy. Previous research had shown that it does not provide significant protection against HIV in its topical vaginal gel form. Research has also shown that topical application of tenofovir is associated with concentrations well above the half-maximal effective concentration for HSV-2.
This double-blinded randomized controlled trial specifically investigated whether pericoital application of tenofovir gel prevented HSV-2 acquisition in women. 422 HSV-seronegative women in rural South Africa were assigned randomly to receive either tenofovir gel or placebo gel. The HSV-2 incidence rate was significantly lower among women who received tenofovir gel over a mean follow-up time of 18 months. On Western blot confirmatory testing, there was again a significantly decreased rate of HSV-2 seroconversion among women assigned to tenofovir gel.
This study is meaningful in buttressing the use of tenofovir vaginal gel in HSV-2 prevention programs around the world, alongside condoms and circumcision; its strength derives from its randomized, double-blinded design. The greatest drawback is that the original trial was designed to assess whether tenofovir gel prevents HIV infection in women. This data was derived from a subset of those women and their tenofovir concentrations at the time of HSV-2 acquisition could not be assessed.
In-Depth [randomized controlled trial]: The larger study from which this was drawn was the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, which involved 889 HIV-negative women in rural South Africa. 422 of the participants were HSV-seronegative and qualified for this secondary analysis. These women were randomized to receive tenofovir or placebo gels, identical in appearance. The overall retention rate during the study was 94.8%. Vaginal tenofovir concentrations were measured once randomly during the follow-up period. Over the study follow-up period of a mean follow-up time of 18 months, there were 87 seroconversions, resulting in overall HSV-2 incidence rate of 15.5 cases per 100 person-years (95% CI, 12.4 to 19.2). The incidence rate ratio comparing incidence of HSV-2 in women receiving tenofovir compared to those receiving placebo was 0.49 (95%CI, 0.30 to 0.77; p=0.003). Correspondingly, the incidence rate ratio comparing Western blot confirmed seroprevalence in these groups was 0.45 (95%CI, 0.23 to 0.82; p=0.005). These results were minimally affected by adjustment for confounding factors including age, parity, use or nonuse of hormonal contraception, and living or not living with a regular partner.
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