Five preliminary studies had showed that it is possible to decrease the amount of HIV in the blood and genital tract when patients are treated with acyclovir for HSV-2, but these studies did not measure whether this meant that acyclovir reduced transmission of HIV. Researchers conducted the trial to find out if the drug would reduce the likelihood of HIV being transmitted from a person infected with both HIV and HSV-2 during sexual intercourse.
In the primary analysis of the Partners in Prevention Transmission Study, researchers determined that there were 41 infections in the acyclovir arm and 43 in the placebo arm, not a significant difference. Acyclover-suppressive treatment reduced the frequency of genital ulcers by 73 percent and the average amount of HIV in the blood (by 0.25 log10copies/milliliter, a reduction of 40 percent), compared to the placebo arm. Although the twice daily use of acyclovir did slow progression of HIV by 17 percent, an effect that was statistically significant, it did not reduce the risk of HIV transmission.
“This study is the first clinical trial to test whether suppressing HSV-2 infection could reduce rates of HIV transmission and HIV disease progression,” said Kenneth H. Fife, M.D., Ph.D., a professor of medicine in the Indiana University School of Medicine, Division of Infectious Diseases and a study co-author. “Because HSV-2 appears to be a major factor in fueling the HIV epidemic, we must better understand this relationship in countries where HIV infection is rampant.”
The study took place at 14 sites in seven countries in eastern and southern Africa,including Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda and Zambia. It began in November 2004 and ended with follow-up of participants in October 2008. The IU School of Medicine’s participation was through the IU-Kenya Partnership program, a program created by the IU and Moi University medical schools. This study was the first large controlled clinical trial to be conducted through the IU-Kenya Partnership.
The Partners in Prevention HSV/HIV Transmission Study was funded by the Bill & Melinda Gates Foundation and led by the University of Washington in Seattle. The study was conducted among 3,408 African couples, in which one partner had HIV and the other did not. In all the couples, the partner who had HIV also had HSV-2 infection. The IU-Kenya Partnership site in Eldoret enrolled 262 couples.
All participants received standard HIV prevention services, which included being supplied with condoms, treated for other sexually transmitted infections, and provided care for HIV infection. All participants received extensive counseling, both individually and as a couple, throughout the study period, on how to reduce the risk of HIV infection.
“The Partners in Prevention Study is a direct assessment of the impact of herpes suppression in HIV transmission,” explained Dr. Connie Celum, the leader of the study and a University of Washington professor of Global Health and Medicine in the Division of Allergy and Infectious Diseases.
“A clinical trial of genital herpes suppression in HIV discordant couples is the most direct way to see if we can make a person less infectious and less likely to transmit HIV to his or her partner,” said Dr. Celum.
The study was double-blinded, randomized and placebo-controlled, meaning that both participants and the care providers did not know which treatment the participants were receiving.
“The study did find that acyclovir significantly reduced genital ulcers due to HSV-2 and modestly reduced HIV levels in the blood, consistent with what the preliminary studies of HSV-2 suppressive treatment had shown. However, it appears that these effects were not sufficient to reduce the risk of HIV transmission,” Celum said.