Tenofovir vaginal gel offers significant protection against HSV-2 infection

Tenofovir gel for the prevention of herpes simplex virus type 2 infection.

Abdool Karim SS, Abdool Karim Q, Kharsany AB, Baxter C, Grobler AC, Werner L, Kashuba A, Mansoor LE, Samsunder N, Mindel A, Gengiah TN, Group CT. N Engl J Med. 2015 Aug 6;373(6):530-9. doi: 10.1056/NEJMoa1410649.

Background: Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections.

Methods: We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2-negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing.

Results: The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P=0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10 000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P=0.14). As confirmed by Western blot testing, 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).

Conclusions: In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women.

Abstract access [1] 

Editor’s notes: Oral tenofovir is widely used to prevent and treat HIV infection, but application of a topical tenofovir vaginal-gel formulation has not been found to be protective against HIV, likely because of low rates of adherence. In contrast, analyses of tenofovir gel protection against HSV-2, herpes simplex virus, has showed some promise. This paper presents additional data and analyses from the CAPRISA004 study which found the modest effect of protection against HIV, but significant protection against HSV-2 (51% effectiveness). A sub-analysis confirmed that those people with higher vaginal tenofovir concentrations were almost three times less likely to acquire the herpes virus than those people with no detectable drug concentration. In the absence of an effective vaccine or cure for HSV-2 infection, pericoital tenofovir gel has the potential to increase the options for HSV-2 prevention, and have an indirect effect on HIV infection. 

Africa [7]
South Africa [8]
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