July 22, 2010
CDC Analysis Presented at the XVIII International AIDS Conference in Vienna, Austria:
Oral Presentation: Kersh, et al., Oral PrEP during mucosal SHIV infection reduces viremia, preserves CD4 counts, and raises potent T cell responses
Pre-exposure prophylaxis (PrEP), the use of HIV treatment medications to protect uninfected individuals from HIV infection, is one of the most promising areas of HIV prevention research. Prior animal research has found multiple PrEP regimens to be effective against infection by monkey viruses similar to HIV, and several human trials are now underway to investigate the safety and efficacy of PrEP in preventing HIV transmission among high-risk groups (including gay and bisexual men, heterosexuals and discordant couples, and injection drug users). These trials are being conducted by CDC, NIH, and other researchers throughout the world, and will be the first to tell us whether PrEP is safe and effective in preventing HIV transmission among humans.
Animal research presented today by CDC's Dr. Ellen Kersh finds that macaques that do become infected with simian human immunodeficiency virus (SHIV, a combination of HIV and a related monkey virus) while receiving PrEP have both lower viral loads and improved immune responses to the virus after becoming infected. This research suggests that even if individuals taking PrEP do become infected, they may still experience other health benefits from having taken antiretroviral (ARV) drugs around the time of infection.
Researchers studied immune responses among eleven macaques that became infected with SHIV rectally as a part of other PrEP studies. Six of the macaques were receiving antiretroviral drugs (Truvada or an experimental tenofovir drug) at the time of infection, and five of the macaques were not receiving any drugs. The animals receiving ARVs continued to receive the drugs and were followed for up to 20 weeks after the initial infection.
The macaques that became infected while receiving PrEP had lower levels of virus in the blood (viral load), as well as better immune responses and function (higher CD4 and T-cell counts) after infection when compared to the macaques not taking PrEP that became infected. However, researchers did not see these benefits last in the animals long-term (i.e., more than six weeks after infection).
While the initial benefits appear promising, the implications of this study for humans are unclear. There are a number of differences between HIV and the monkey form of the virus (SHIV), as well as in how monkeys respond to the virus. Human data will be needed to determine what role PrEP may play in the long-term immune response of humans infected with HIV while taking PrEP. Researchers believe that if PrEP can help to control the virus early on, it may lead to better clinical outcomes later in the course of infection. Having lower viral loads and higher CD4 counts after infection could delay the need to initiate antiretroviral treatment, as well as reduce transmission to partners, and may also delay disease progression.
Separately, the human PrEP trials currently underway are monitoring aspects of immune function and viral load among participants that become infected during the course of the trial. Results from these trials will help determine how animal data correlate to humans, and will also help guide next steps in research and practice.