A presentation at the International AIDS Conference in Washington, D.C. in August has concerned HIV prevention activists, because researchers found that the antiretroviral (ARV) drug Selzentry (maraviroc) didn’t work as well as they hoped at preventing infection from the monkey version of HIV in macaque monkeys.
Right now, the only ARV approved to prevent HIV transmission is Truvada (tenofovir disoproxil fumarate + emtricitabine). The concept is that HIV negative people take Truvada every day to avoid becoming infected due to sexual exposure to the virus. This method is called pre-exposure prophylaxis (PrEP).
One of the main concerns with Truvada for PrEP is that if a person becomes infected with HIV while taking it, their virus could quickly develop resistance to the drug—and Truvada is one of the ARVs that government guidelines recommend that people take first. Selzentry, on the other hand, is not a preferred drug and is rarely used. If someone became infected while taking it, this would not severely limit his or her treatment choices.
A safety study of Selzentry in humans just got underway, but in the meantime scientists have been studying the drug as PrEP in macaques. The way Selzentry works is by binding tightly to a receptor, called CCR5, on the surface of cells that HIV must use to infect the cells. When all of the CCR5 receptors are blocked, HIV can’t enter the cell and infect it.
Unfortunately, despite high levels of Selzentry found in the rectal tissue of the macaques that were treated with the drug, most of them ultimately became infected with the monkey version of HIV when they were exposed to it.
While this is disappointing, experts point out that all is not lost. This is because previous studies have found that Selzentry doesn’t stay bound to CCR5 on the immune cells of monkeys as well as it does in humans. This means that humans might be protected much better than monkeys. Ultimately, only human studies will reveal whether Selzentry is a good candidate for PrEP, but the news about its failure to protect macaques from infection is sobering.