Tenofovir gel use associated with lower HSV-2 risk in women

The risk of acquiring herpes simplex virus type 2 (HSV-2) was reduced by 46% (aIRR:0.54, 95%CI:0.30-0.97, p = 0.038) among women who regularly used the vaginal gel containing tenofovir, according to a secondary analysis of the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial presented at the HIV Research for Prevention conference (R4P) in Cape Town, South Africa.

There was no significant difference in the age, marital status, country, practice of anal sex, HIV status or hormonal contraceptive use between those who acquired HSV-2 and those who did not.

“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 Dr Jeanne Marrazzo, who was presenting the study on behalf of the VOICE study team.

Glossary

herpes simplex virus (HSV)

A viral infection which may cause sores around the mouth or genitals.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

oral

Refers to the mouth, for example a medicine taken by mouth.

microbicide

A product (such as a gel or cream) that is being tested in HIV prevention research. It could be applied topically to genital surfaces to prevent or reduce the transmission of HIV during sexual intercourse. Microbicides might also take other forms, including films, suppositories, and slow-releasing sponges or vaginal rings.

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 sexual 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 Dr Marrazzo.

Although the phase 2B, randomised, double-blind VOICE study was designed to test the safety and efficacy to prevent HIV of daily Truvada (tenofovir 300mg plus emtricitabine 200mg) as pre-exposure prophylaxis (PrEP), daily tenofovir (300mg) as PrEP, and a 1% tenofovir-containing gel (similar to that used in the CAPRISA 004 study) to be used as a vaginal microbicide, the team amended the protocol to 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 by 51% compared to placebo. Other studies have shown that daily tenofovir plus emtricitabine PrEP did not reduce HSV-2 acquisition among men who have sex with men (MSM), but that it 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 blood. Adherence in the original VOICE trial was poor with tenofovir detected in less than a quarter of samples from women asked to use the tenofovir gel.

The analysis found that HSV-2 incidence was 20.1% (95%CI: 15.9-25.2) in women who did not use the gel, compared to 11.5% (95%CI: 6.4-18.9) in women who used the gel regularly. Of the 1004 women assigned to use the tenofovir gel, 566 were HSV-2 negative at the time of enrolment. In follow-up of 527 of these women, 92 women acquired HSV-2 (an overall incidence of 17.9%, 95%CI: 14.5-22.0 over 513 person-years), 77 of whom had no detectable drug in their blood samples versus 15 whose blood levels indicated regular use of the gel. A comparison of the 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%, n = 90 of 529) and those who received the tenofovir gel but had no tenofovir plasma detected in their blood samples (19.2%, n = 77 of 402) (aIRR:1.11, 95%CI:0.82-1.51, p = 0.499).

Dr 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 III 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 anticipated to be available early next year.

References

Mazzarro J et al. Association of tenofovir detection with reduced risk of herpes simplex virus Type-2 (HSV-2) acquisition in the VOICE (MTN003) study. HIV Research for Prevention Conference (HIV R4P), abstract OA10.06 LB, Cape Town, South Africa, 2014.

To view the slides and listen to the audio of this presentation, go to http://webcasts.hivr4p.org/console/player/25067?mediaType=audio&