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A recently concluded clinical trial funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has found that the anti-herpes drug acyclovir did not reduce the risk of acquiring sexually transmitted HIV when given to men and women infected with herpes simplex virus-2 (HSV-2). Multiple studies indicate that people infected with HSV-2 are at increased risk of acquiring HIV. Researchers have speculated that the use of acyclovir, a safe and widely used herpes drug, could reduce HIV transmission by suppressing HSV-2 and preventing genital sores and breaks in the skin.
Results from the Phase III clinical study, which was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and conducted by the NIAID-funded HIV Prevention Trials Network (HPTN), were presented this week at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston. The study, known as HPTN 039, is the largest clinical study ever conducted to examine herpes suppression as a possible means of reducing the risk of HIV transmission.
NIAID director Anthony S. Fauci, MD, says, "Although HPTN 039 did not yield a successful result with regard to herpes suppression as a possible tool for HIV prevention, the concept of treating and preventing sexually transmitted infections as a possible tool in HIV prevention remains an important one. We will continue to work to understand how HSV-2 and other STIs increase the risk of HIV infection, and to develop new interventions that might play a role in HIV prevention."
HSV-2, one of the most common sexually transmitted infections worldwide, is especially prevalent in areas with high rates of HIV infection. Most people who are infected with HSV-2 do not know they have the virus because symptoms can be mild or nonexistent. Some infected individuals have recurring sores and breaks in the skin of the genital region, which can make it easier for these individuals to acquire HIV. Additionally, active HSV-2 infection attracts specific immune system cells to the genital region that are easily infected with HIV.
People with genital herpes should be aware that this infection increases their risk for HIV infection. It is critical all individuals especially those with herpes know if they are infected with HIV and take measures to protect themselves from infection with HIV and other sexually transmitted diseases.
The HPTN 039 study was launched in October 2003 under the leadership of Connie Celum, MD, and Anna Wald, MD, of the University of Washington in Seattle. It was designed to determine if acyclovir could reduce an HSV-2 infected person's risk of acquiring HIV infection. The clinical trial was conducted at nine sites in Peru, South Africa, the United States, Zambia and Zimbabwe, and involved 3,172 total HSV-2-infected volunteers, including heterosexual women as well as men who have sex with men. The women were enrolled at the three African study sites, and the men at the six study sites in Peru and the United States.
The participants received either a twice-daily, 400-milligram (mg) dose of acyclovir tablets (800 mg total per day) the standard treatment regimen for suppressing genital herpes or placebo tablets. Throughout the course of the study, volunteers were extensively counseled on how to avoid exposure to HIV and were supplied with condoms.
The researchers found no evidence that the standard acyclovir regimen prevents HIV infection among HSV-2 infected people. Specifically, there was a 3.9 percent HIV incidence rate (75 cases) among the 1,637 participants who received acyclovir, while there was a 3.3 percent HIV incidence rate (64 cases) among the 1,640 participants who received placebo.
"The difference in HIV rates in the acyclovir and placebo group is not statistically significant, indicating that when acyclovir is used twice-daily at the 400 mg dose, the drug does not prevent HSV-2-infected individuals from becoming infected with HIV," says Celum. "More research is needed to understand ways to reduce HIV susceptibility among persons with HSV-2."
The study did, however, provide additional evidence that acyclovir reduces the occurrence of genital sores: the volunteers who received acyclovir had a 37 percent decrease in genital ulcer incidence and a significantly lower proportion of ulcers due to HSV-2.
"The study answered the scientific questions it was designed to answer," says Wald. "The sites were able to recruit and retain a large number of volunteers, who maintained a high level of adherence to the twice-daily drug regimen. While we are disappointed with the results, the study was well-conducted and provides a clear answer about using acyclovir to reduce the risk of becoming HIV-infected."
The study participants have been informed of the findings and are being counseled on the continued need to avoid HIV exposure. Volunteers who became infected with HIV during the trial have been referred for appropriate medical care and treatment.
The HPTN is led by Family Health International in Research Triangle Park, N.C., HPTN clinical laboratory located at Johns Hopkins University in Baltimore, and the Statistical Center for HIV/AIDS Research and Prevention at the Fred Hutchinson Cancer Research Center in Seattle.
Source: National Institutes of Health