A recently completed international multi-center clinical trial has found that acyclovir, a drug widely used as a safe and effective treatment to suppress herpes simplex virus-2 (HSV-2), which is the most common cause of genital herpes, does not reduce the risk of HIV transmission when taken by people infected with both HIV and HSV-2.
The majority of people with HIV infection also have HSV-2 infection.
Multiple studies have shown that frequent genital herpes recurrences increase the amount of HIV in the blood and genital tract. The HIV virus is also shed from genital herpes ulcers and individuals with such ulcers transmit HIV to others more efficiently.
Led by the University of Washington in Seattle and funded by the Bill & Melinda Gates Foundation, the Partners in Prevention HSV/HIV Transmission Study was conducted among 3,408 African HIV discordant 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 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.”
The study also determined whether acyclovir can slow HIV disease progression among individuals with HIV and HSV-2 who also have CD4 T-cell counts that are too high for HIV antiretroviral treatment under current national guidelines
“Although the primary outcome of reducing HIV transmission was not observed, the study yielded important information that will inform HIV prevention research in a number of ways,” Celum said. “Most importantly, we have demonstrated that interventions must achieve a bigger reduction in HIV levels in order to reduce HIV transmission, especially among persons with high HIV levels. This was an ambitious study, which required testing of an estimated 50,000 couples of unknown HIV status in Africa to recruit the 3,408 HIV discordant couples who volunteered to enroll in the study.”
HSV-2 is one of the most common sexually transmitted infections worldwide and is especially prevalent in areas with high rates of HIV infection, with up to 90% of individuals who have HIV also being infected with HSV-2.
The Partners in Prevention HSV/HIV Transmission Study is the first clinical trial to directly test whether suppressing HSV-2 infection could reduce rates of HIV transmission and HIV disease progression.
“Based on the findings from this study, we now better understand the relationship between HIV levels and HIV transmission. This shows us that the ‘bar’ is higher than we anticipated for the amount of reduction in HIV levels needed in order to reduce HIV infectiousness and transmission. This is relevant for other interventions,” Celum said, “such as anti-retroviral drugs to treat HIV, treatment of co-infections such as malaria, and therapeutic HIV vaccines. “
This understanding is a major contribution to HIV research that will help guide our search for new HIV prevention and treatment strategies.
Source: University of Washington, USA