Tenofovir Gel May Prevent Herpes Simplex Virus in Women
Daily application of a 1% tenofovir gel formulation—under investigation as a new form of HIV pre-exposure prophylaxis—appears to reduce women’s risk of acquiring herpes simplex virus type-2 (HSV-2). HSV-2 is the virus that causes genital herpes. Currently, no vaccines or medications to prevent HSV infection are available.
The risk of acquiring HIV when exposed to the virus is three times higher with HSV-2 infection, even in the absence of HSV-2 symptoms. Tiny ulcerations in the skin caused by HSV-2 provide an entry point for HIV. An estimated 16% of people—or about 1 in 6—between the ages of 14-49 are infected with HSV-2 in the U.S., making primary prevention of HSV-2 an important strategy to reduce increased risk of HIV associated with HSV-2.
Jeanne Marrazzo, MD, PhD, Professor in the Division of Allergy and Infectious Diseases in the Department of Medicine at the University of Washington, presented new data analyses from the Vaginal and Oral Interventions to Control the Epidemic (VOICE) study at the HIV Research for Prevention conference held in October in Cape Town, South Africa.
In the study, 1,004 women across Uganda, South Africa, and Zimbabwe were instructed to apply the vaginal gel containing tenofovir (1%) on a daily basis to prevent HIV. Tenofovir is one component of the combination pill Truvada, used in HIV pre-exposure prophylaxis (PrEP). Because adherence to prevention regimens affects outcomes, the researchers in this study measured tenofovir levels in biologic samples (blood samples and vaginal swabs) to know for sure which women were actually using the medication. They then compared the incidence rate of new HSV-2 infections between women with evidence of tenofovir in their system and women without tenofovir in their system.
Researchers measured levels of tenofovir in the blood after three months and from a vaginal swab after six months. At the beginning of the study, 56% of the original sample (a total of 532 women) were susceptible to HSV-2 infection (i.e., were HSV-2 negative).
After three months, there were a total of 92 new HSV-2 infections. Fifteen new infections were in women who had a detectable level of tenofovir in their blood, while 77 were among women who were not using the tenofovir gel.
A difference in HSV-2 risk between women using and not using the medication was evident. Only about a quarter of women with access to the tenofovir gel had detectable tenofovir levels after three months. Women with detectable tenofovir in their blood after three months were about half as likely to acquire HSV-2 over time.
Marrazzo noted that her team controlled for a number of factors that could be associated with adherence, but that the relationship was still evident even after adjusting for things like age, marital status, having more than two partners, anal sex, HIV status, and hormonal contraceptive use. This finding points to the robustness of the study’s findings.
At the six month time point, Marrazzo’s team found a similar trend using vaginal swab samples to measure medication use. Close to 50% of the women with access to the tenofovir gel had detectable tenofovir levels.
Among the 89 new HSV-2 infections, 32 came from women with detectable tenofovir levels and 57 came from women without detectable tenofovir levels. Although there was a higher incidence rate of tenofovir-users compared to non-users (19.7 versus 14.1) this difference didn’t reach statistical significance.
This is not the first evidence that a vaginal tenofovir gel can prevent HSV-2 infection. The landmark CAPRISA 004 study, which paved the way for HIV prevention microbicide research and development, found that vaginal application of a tenofovir gel before and after sex reduced risk of HSV-2 infection by 51%. The number of women included in CAPRISA 004 study was relatively small, however, and the variation in documented effectiveness was large.
The VOICE HSV-2 data analysis is still ongoing, and the researchers are in the process of preparing scientific journal articles documenting their findings for publication in 2015. Thus, final conclusions from this part of the study are still pending, notes Zvavahera Chirennje, MD, Professor in the Department of Obstetrics and Gynecology at the College of Health Sciences at the University of Zimbabwe, lead researcher for VOICE.