VOICE Trial: Daily Vaginal Tenofovir Gel Use Reduced Genital Herpes Risk in Women

Genital herpes simplex virus type-2 (HSV-2) infection increases the risk of acquiring and transmitting HIV, particularly in areas of sub-Saharan Africa where HIV is highly prevalent. A new study suggests that women who consistently used a vaginal tenofovir (TFV) gel for pre-exposure prophylaxis (PrEP) saw a reduced risk of HSV-2 and HIV-1 acquisition.

The new manuscript, published on February 11, 2019 in The Journal of Infectious Diseases, provides information on the VOICE study, a large, randomized, placebo-controlled trial of HIV-1 PrEP products, including oral tenofovir disoproxil fumarate (TDF) and vaginal TFV 1% gel, which enrolled reproductive-aged women.

The trial enrollment was conducted across 15 sites in South Africa, Uganda, and Zimbabwe from September 2009 to June 2011. Enrolled participants were women aged 18 to 45 years who were neither pregnant nor breastfeeding and had normal renal, hematologic, and hepatic function. The participants were also required to have reported recent vaginal intercourse and current use of effective contraception. Participants were assigned to 1 product for daily use and tested for sexually transmitted infections at enrollment, annually, and when indicated.

“No biomedical prevention method currently exists for HSV-2, the most common cause of genital herpes,” explained study co-author Jeanne Marrazzo, MD, MPH, FACP, FIDSA, director of the Division of Infectious Diseases and professor of medicine at University of Alabama Birmingham, in an interview with Contagion^®. “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. We are really interested in combination prevention products that can impact both HSV-2 and HIV acquisition.”

A total of 1004 enrolled participants were randomized to receive TFV gel, of whom 438 (44%) were HSV-2 seropositive and 566 (56%) were seronegative. Among women who were seronegative at enrollment, 92 acquired HSV-2 over a median time of 1 year, and investigators found that adherence to study products was low overall, especially among younger, unmarried women who had the highest incidence of HIV-1 and HSV-2.

In a secondary analysis though, investigators used plasma measurement of TFV to measure product use and detection of TFV in the plasma of 130 (24%) participants. Investigators found that overall regular use of TFV gel was associated with reduction in HSV-2 acquisition by 40%.

The findings, say the investigators, add to evidence supporting the effectiveness of vaginal TFV gel in reducing women’s risk of HSV-2 acquisition, and investigators found a similar protective effect of TFV gel on HIV-1 infection. Dr. Marrazzo notes that certain VOICE participants were more likely to stick to the daily TFV gel regimen.

“Women were more likely to be adherent if they were in stable relationships, older, had more children, and earned their own income—all things that were also independently associated with lower risk of HIV,” said Dr. Marrazzo, noting that vaginal rings that release TFV could be another approach to slow the acquisition of HSV-2 and HIV in women. “We need products that can address both infections to maximize protective impact.”