The race is on to prevent the spread of herpes simplex virus type 2 (HSV-2) infection, the most common cause of genital ulcer disease. In 2012, about 417 million sexually active adults ages 15-49 years had an existing prevalent HSV-2 infection.1 Genital ulcerative disease caused by herpes makes it easier to transmit and acquire HIV infection. Data indicate there is an estimated twofold to fourfold increased risk of acquiring HIV, if exposed to HIV when genital herpes is present.2-5
Results of a South African study indicate that pericoital application of tenofovir gel reduced acquisition of HSV-2.2 The study is a substudy of a double-blind, placebo-controlled, randomized trial, CAPRISA 004. That study was the first to show that a microbicide could reduce the risk of HIV in women.6 Follow-on African Consortium for Tenofovir Studies (FACTS) reported in February 2015 that its results did not confirm the HIV protective effect of tenofovir gel shown in the CAPRISA 004 trial. While the gel showed a protective effect in women who used it consistently as prescribed by the study protocol, high adherence in the overall study population was too low to show gel effectiveness in the FACTS trial.7
In the current study, researchers conducted a subgroup analysis of 422 HSV-2-negative women in the CAPRISA 004 study. Tenofovir and placebo gels, dispensed in prefilled vaginal applicators, were used, with instructions to use one dose within 12 hours before sex and a second dose as soon as possible within 12 hours after sex, with a maximum of two doses per 24 hours. Mean follow-up duration was 18 months.
Data indicates the HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among women assigned to tenofovir gel, compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among the placebo group (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P = 0.003). There were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P = 0.005). Risk reduction was higher among women who used the gel frequently compared with those who used it less often.5
Given the anti-HSV-2 activity of tenofovir, Rachel Bender Ignacio, MD, MPH, senior fellow in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center in Seattle, and others evaluated the efficacy of tenofovir on reducing HSV-2 shedding and symptomatic genital lesions in HSV-2 infected women.8
Researchers evaluated viral shedding of viral DNA and lesion rate in 64 women enrolled through the University of Washington Virology Research Clinic during a four-week lead-in phase in which they did not receive treatment, and a five-week trial of oral tenofovir, vaginal topical tenofovir, or placebo. No statistically significant differences were observed before and during treatment in the oral tenofovir arm overall. However, in highly adherent women, the oral formulation reduced symptomatic and asymptomatic shedding and lesions by about 25%, while the oral and vaginal gel products reduced viral DNA shed by half a log.8
While tenofovir has the added benefit of preventing HSV-2 acquisition in those who seek HIV prevention strategies, there is little role for tenofovir or emtricitabine/tenofovir disoproxil fumarate (Truvada, Gilead Sciences, Foster City, CA) in persons who are not also desiring HIV pre-exposure prophylaxis, says Bender Ignacio. Also, the way forward will likely consist of dually formulated products, she notes.
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Looker KJ, Magaret AS, Turner KM, et al. Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012. PLoS One 2015; 10(1):e114989.
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Freeman EE, Weiss HA, Glynn JR. Herpes simplex virus 2 infection increases HIV acquisition in men and women: Systematic review and meta-analysis of longitudinal studies. AIDS 2006; 20(1):73-83.
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Barnabas RV, Celum C. Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV-1: New insights and interventions. Curr HIV Res 2012; 10(3):228-237.
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Corey L, Wald A, Celum CL, et al. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: A review of two overlapping epidemics. JAIDS 2004; 35(5): 435-445.
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Abdool Karim SS, Abdool Karim Q, Kharsany AB, et al. Tenofovir gel for the prevention of herpes simplex virus type 2 infection. N Engl J Med 2015; 373:530-539.
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Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329:1168-1174.
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Rees H, Delany-Moretlwe SA, Lombard C, et al. FACTS 001 Phase III trial of pericoital tenofovir 1% gel for HIV prevention in women. Presented at the 2015 Conference on Retroviruses and Opportunistic Infections. Seattle; February 2015.
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Bender Ignacio RA, Perti T, Magaret AS, et al. Oral and vaginal tenofovir for genital herpes simplex virus type 2 shedding in immunocompetent women: A double-blind, randomized, cross-over trial. J Infect Dis 2015; doi:10.1093/infdis/jiv317.
