Even healed genital herpes increases HIV risk

Kathleen Blanchard's picture

Scientists now understand an important factor about how HIV is transmitted. A new study shows that individuals with healed genital herpes sores are at higher risk of contracting the HIV virus. The findings show that even when genital herpes has been treated, and the lesions have disappeared, risk of HIV is still higher for individuals with genital herpes.

The study appears online in the August 2 edition of Nature Medicine. The environment of immune cells associated with genital herpes is a favorable environment for the HIV virus, even after healing has occurred and herpes has been treated with oral acyclovir. The environment that persists after a genital herpes sore has healed is still conducive to the HIV virus according to findings from the study.

Partial funding for the study came from the National Institute of Allergy and Infectious Diseases (NIAID). According to NIAID Director Anthony S. Fauci, M.D. "Understanding that even treated HSV-2 infections provide a cellular environment conducive to HIV infection suggests new directions for HIV prevention research, including more powerful anti-HSV therapies and ideally an HSV-2 vaccine.

Dr. Fauci says the study explains why antiviral drugs to treat genital herpes do not seem to reduce the risk of HIV infection. "The findings of this study mark an important step toward understanding why HSV-2 infection increases the risk of acquiring HIV and why acyclovir treatment does not reduce that risk.”

Genital herpes increases risk of HIV two to three-fold, and is one of the most common sexually transmitted diseases in the world.

Previous thinking linked skin breaks from genital herpes to increased risk of HIV, but recent studies failed to show that treatment for genital herpes simplex 2 virus (HSV-2) with acyclovir reduces the risk.


Lawrence Corey, M.D of the Fred Hutchinson Cancer Research Center led the study in conjunction with Jia Zhu, Ph.D. and Anna Wald, M.D., M.P.H., of the University of Washington. According to Dr. Corey, "We hypothesized that sores and breaks in the skin from HSV-2 are associated with a long-lasting immune response at those locations, and that the response consists of an influx of cells that are a perfect storm for HIV infection. We believe HIV gains access to these cells mainly through microscopic breaks in the skin that occur during sex”. Instead they found out even more - HIV also has an affinity for attaching to the type of immune cells that linger even after genital herpes sores disappear.

The scientist found out three important ways that genital herpes contributes to increased risk of HIV by taking multiple biopsies from eight HIV negative men and women during a herpes outbreak, after healing, and then four to eight weeks after genital herpes sores had disappeared. They again took biopsies after treatment with acyclovir in four of the participants when genital herpes reappeared. They also took biopsies of normal skin for comparison.

They study showed that CD4+T cells that HIV usually infect hang around at the site of genital herpes even after they have healed, in concentrations as high as 37 times greater than normal. They also found that many of the CD4 + T cells contained twice as many proteins used by HIV to enter cells, called CCR5 or CXCR4. High concentrations of DC-SIGN, a transporter of HIV into CD4+T cells were also present even after treatment with acyclovir, producing an extremely favorable environment for infection with HIV.

The last finding relating to genital herpes and increased risk of HIV included fast replication of the virus where genital herpes sores had been healed. HIV replicated 3 to 5 times faster in tissue taken from healed genital herpes site compared to tissue taken from controlled tissue sites.

The authors say genital herpes, caused by the HSV- 2 virus “provides a wide surface area and long duration of time for allowing HIV access to more target cells, providing a greater chance for the initial 'spark' of infection.”

Finding ways to reduce HIV transmission means boosting immunity at the site of genital herpes. The study authors suspect that other sexually transmitted diseases also create an immune environment conducive to HIV transmission. The study explains why sexually transmitted infections increase risk of HIV.

Nature Medicine DOI: 10.1038/nm2006 (2009).