Cancer drug reduces SIV reservoir in macaques

At 14 days postinfection, rhesus macaques received either antiretroviral therapy (ART) alone or the same treatment combined with venetoclax, a clinically approved cancer medication. In the Emory University study, the combination reduced simian immunodeficiency virus (SIV)-infected CD4+ T cells faster than ART alone and kept infected-cell levels lower for months after venetoclax was stopped.

The drug is aimed at Bcl-2, a protein that regulates whether cells live or die and promotes the survival of cancer cells. The Emory team says Bcl-2 also helps sustain HIV reservoirs. By blocking it as ART began, researchers tested whether infected cells could be removed before they became part of the long-lived reservoir that persists despite treatment.

Mirko Paiardini, senior author and chief of the Microbiology and Immunology Division at Emory’s National Biomedical Research Center, led the work with first author Tomas Raul Wiche Salinas. The researchers describe the result as a proof of concept in a nonhuman primate model. They gave venetoclax for just 10 days, while continuing ART, and observed that the lower level of infected cells lasted for months after the drug was withdrawn.

The boundary of the result is clear. This was not a cure in people, and the team is still assessing whether a longer venetoclax treatment would have a greater effect and which cellular mechanisms allow infected cells to survive despite Bcl-2 inhibition. Paiardini says the macaques were vital because they carry latently infected cells that persist during long-term ART and represent human immune responses in the preclinical work.

For people living with HIV, the near-term consequence is clinical testing, not a newly established cure: two clinical trials are underway to test venetoclax in humans. The study’s practical contribution is narrower and more tangible—a cancer drug already approved for clinical use has reduced the viral reservoir in macaques when paired with ART, giving researchers a treatment to test rather than a mechanism to search for from scratch.