HIVR4P 2014: Tenofovir Gel Associated with Lower Herpes Simplex Risk for Women

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The risk of acquiring herpes simplex virus type 2 (HSV-2) was reduced by 46% among women who regularly used a vaginal gel containing tenofovir, according to a secondary analysis of the VOICE trial presented at the HIV Research for Prevention conference (R4P) this week in Cape Town. There was no significant difference in the age, marital status, country, practice of anal sex, HIV status, or hormonal contraceptive use between women who acquired HSV-2 and those who did not.

[Produced in collaboration with Aidsmap.com]

"The findings provide additional evidence that tenofovir gel, a product developed to protect against HIV, could potentially help in preventing one of the most prevalent sexually transmitted infections in sexually active women in sub-Saharan Africa," said Jeanne Marrazzo, who was presenting the study on behalf of the VOICE (Vaginal and Oral Interventions to Control the Epidemic) study team.

No biomedical prevention method currently exists for HSV-2, the most common cause of genital herpes. Women are especially susceptible to infection because it is more easily transmitted from an infected man to his female sex partner than from a woman to a man. "Because HSV-2 infection also greatly enhances the risk of acquiring and transmitting HIV, a product that protects against HSV-2 could have an important public health impact," said Marrazzo.

The Phase 2b, randomized, double-blind VOICE study was designed to test the safety and efficacy of daily Truvada (300 mg tenofovir + 200 mg emtricitabine) and daily tenofovir alone as pre-exposure prophylaxis (PrEP) against HIV infection, as well as a 1% tenofovir-containing gel (similar to that used in the CAPRISA 004 study) as a vaginal microbicide. However, the team amended the protocol to also explore whether any of these products protect women from acquiring HSV.

This was done in response to the CAPRISA 004 study, which unexpectedly found that tenofovir gel also reduced the risk of HSV-2 infection by 51% compared to placebo. Other studies have shown that daily oral tenofovir/emtricitabine PrEP did not reduce HSV-2 acquisition among men who have sex with men, but that is did reduce HSV-2 acquisition by 30% in serodiscordant couples in the Partners PrEP study.

In this secondary analysis, researchers focused on women with high adherence to the tenofovir gel according to their pharmacokinetic results, which measures the levels of the drug in their blood. Adherence in the original VOICE trial was poor, with tenofovir detected in less than one-quarter of samples from women asked to use the tenofovir gel.

The analysis found that HSV-2 incidence was 20.1% among women who did not use the gel, compared to 11.5% among women who used the gel regularly. 566 of the 1004 women assigned to use tenofovir gel were HSV-2 negative at the time of enrollment. In follow up of 527 of these women, 92 acquired HSV-2 (an overall incidence of 17.9% over 513 person-years). Among those who acquired HSV-2, 77 had no detectable tenofovir in their blood samples versus 15 with blood levels indicating regular use of the gel. A comparison of pharmacokinetic levels in participants’ blood samples were taken from both their first quarterly visit and when they exited the study 12 months later.

There was also no significant difference in the number of incident HSV-2 infections between the group who received a placebo vaginal gel (17.0%,  or 90 out of 529 women) and those who received tenofovir gel but had no tenofovir detected in their blood samples (19.2%, or 77 out of 402).

Marrazzo admitted that one of the limitations of the study is that it is a secondary analysis based on a subset of participants, which is subject to bias.

While the results of this study are encouraging, additional data are still needed. FACTS 001, a Phase 3 trial that tested tenofovir gel used before and after sex (the same regimen as in CAPRISA 004), was designed specifically to determine whether the gel was safe and effective in reducing the risk of HSV-2 and HIV among 2059 women in South Africa. These results are expected to be available early next year.

10/31/14

Reference

J Mazzarro, L Rabe, C Kelly, et al. Association of Tenofovir (TFV) Detection with Reduced Risk of Herpes Simplex virus Type-2 (HSV-2) Acquisition in the VOICE (MTN 003) Study. HIV Research for Prevention (HIV R4P). Cape Town, South Africa, October 28-31, 2014. Abstract OA10.06 LB.

Other Source

Microbicide Trials Network. New Results from VOICE Associates Tenofovir Gel Use with Lower HSV-2 Risk in Women. Press release. October 28, 2014.