NIH Research Matters
August 17, 2009
Why Genital Herpes Boosts the Risk of HIV Infection
Scientists have discovered why people who develop genital herpes sores are at higher risk of contracting HIV despite successful treatment of the lesions. The new insight may lead to better strategies for HIV prevention.
Genital herpes, caused by the herpes simplex virus type 2 (HSV-2), is one of the most common sexually transmitted infections worldwide. It is also associated with a 2- to 3-fold increased risk for HIV infection. Some people infected with HSV-2 suffer from recurring sores and breaks in genital skin. Researchers hypothesized that these lesions account for the higher risk for HIV. However, recent clinical trials that successfully treated genital herpes lesions with the anti-viral drug acyclovir didn't reduce the risk of HIV infection.
A team led by Dr. Lawrence Corey and Dr. Jia Zhu of the Fred Hutchinson Cancer Research Center and Dr. Anna Wald of the University of Washington sought to understand why genital herpes boosts the risk of HIV infection even after treatment with oral acyclovir and the healing of genital lesions. Their work was funded by NIH's National Institute of Allergy and Infectious Diseases (NIAID) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
The researchers obtained biopsies of genital skin tissue from 8 HIV-negative men and women who were infected with HSV-2. The biopsies were taken when genital herpes sores appeared, when they healed, and then between 2 and 8 weeks after they had subsided. In the second phase of the study, 4 of the 8 patients were treated with acyclovir at the beginning of a herpes outbreak. Biopsies were taken from when lesions appeared to 20 weeks after they had healed. For comparison, the investigators took biopsies from the same patients of genital tissue that did not have herpes lesions.
The scientists reported in the August 2009 issue of Nature Medicine that CD4+ T cells, which HIV targets and infects, appeared at the sites of healed genital HSV-2 lesions at concentrations 2 to 37 times greater than in unaffected genital skin. Moreover, the CD4+ T cells at healed lesion sites expressed higher levels of 2 cell-surface receptors—CCR5 and CXCR4—that HIV uses to enter T cells. Compared to control tissue, the sites of healed genital herpes lesions also had a significantly higher concentration of immune cells known to ferry HIV particles to CD4+ T cells, whether or not the patient was treated with acyclovir.
In further experiments, the scientists found that HIV replicates 3 to 5 times as quickly in cultured tissue from the sites of healed HSV-2 lesions as in cultured tissue from control sites.
These results suggest that HSV-2 lesions create an ideal scenario for the rapid spread of HIV infection. Other sexually transmitted infections may create a similar cellular environment favorable to HIV infection, potentially explaining why sexually transmitted infections are general risk factors for HIV.
“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,” says NIAID Director Dr. Anthony S. Fauci.
NIH Research Matters
Bldg. 31, Rm. 5B64A, MSC 2094
Bethesda, MD 20892-2094
About NIH Research Matters
Harrison Wein, Ph.D., Editor
Vicki Contie, Assistant Editor
NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.