Tenofovir Gel Reduces Risk for Herpes Simplex Virus Type 2 Acquisition

Among tenofovir (TFV) gel users, detection of plasma tenofovir may be associated with a reduced risk for herpes simplex virus type 2 (HSV-2) acquisition, according to a study published in the Journal of Infectious Diseases.

Genital infection with HSV-2 is a major health concern for women of reproductive age and increases the risk for both HIV transmission and acquisition. In areas with the highest incidence of HIV, HSV-2 is most prevalent, especially in sub-Saharan Africa. Most cases of genital herpes are asymptomatic or cause unrecognized infection; although antiviral treatment reduces the risk for sexual transmission, genital HSV shedding can still occur. However, there is no vaccine available presently. Tenofovir is a reverse transcriptase inhibitor that has in vitro anti-HSV-2 activity, but also has a high E90. To overcome the high E90, vaginal application has been used with results in vaginal concentrations 1000-fold higher than those achieved with daily oral tenofovir. A previous study showed that vaginal tenofovir gel (1%) reduced the risk for HSV-1 acquisition by 51%.

VOICE was a large trial of oral tenofovir, oral tenofovir-emtricitabine, and vaginal tenofovir 1% gel as HIV preexposure prophylaxis in reproductive-aged women in South Africa, Uganda, and Zimbabwe. Women participants were asked to use the study products daily; however, adherence was low. In a secondary analysis, women who were adherent to tenofovir gel had a decreased risk for HIV acquisition; tenofovir measures in plasma at the first quarterly visit was used to measure gel use. Therefore, this study assessed whether that subgroup of women adherent to tenofovir gel in VOICE had a reduced rate of HSV-2 acquisition compared with those who were not adherent.

A total of 532 women at risk for HSV-2 had both first quarter plasma tenofovir and end-of-study HSV-2 serology available. The primary endpoint was HSV-2 infection, measured by seroconversion via a Western blot assay. Plasma samples from the enrollment visit were screened for existing HSV-2 infection to identify women susceptible to HSV-2 infection (index values <3.5).

During the follow-up period, 92 incidence HSV-2 cases occurred in 92 women: 77 women with no plasma tenofovir detected and 15 with plasma tenofovir (incidence, 20.6 vs 11.9, respectively). After the hazard ratio was adjusted for site, age, sexual partners, hormonal contraception, anal sex, and HIV status, results showed that plasma tenofovir detection was associated with a reduction in HSV-2 acquisition by 40% (hazard ratio, 0.33-1.08); however, this was not statistically significant (P =.086).

Overall, the study authors concluded that, “With our finding of a similar protective effect of [tenofovir] gel on HIV-1 infection using an analogous [pharmacokinetic]-based analysis, these data support further study of delivery of [tenofovir] or derivatives to cervicovaginal tissue as a potential means of slowing the HSV-2 epidemic.”

Reference

Marrazzo JM, Rabe L, Kelly C, et al. Tenofovir gel for prevention of herpes simplex virus type-2 acquisition: findings from the VOICE trial [published online February 11, 2019]. J Infect Dis. doi: 10.1093/infdis/jiz045/5315462