Cancer drug reduces viral reservoir, advancing HIV cure research

Clinical takeaway: Targeting BCL-2 with venetoclax may offer a new way to reduce the viral reservoir that makes lifelong HIV treatment necessary. If ongoing human trials confirm safety and effectiveness, the approach could become an adjunct to ART and support future treatment-free remission strategies.

Antiretroviral therapy (ART) can suppress HIV indefinitely but cannot eliminate the long-lived infected cells in which the virus remains hidden. These cells form the viral reservoir, allowing HIV to return if treatment is stopped.

Venetoclax, an oral medication approved for certain blood cancers, may provide a way to target these persistent cells. The drug blocks BCL-2, a protein that helps cells survive. HIV-infected cells appear to rely on BCL-2 to avoid cell death and remain in the body despite ART.

Researchers tested the approach in 24 rhesus monkeys infected with simian immunodeficiency virus (SIV), which closely resembles HIV. Adding 10 days of venetoclax when ART began produced a rapid decline in cells carrying intact virus.

After treatment, the concentration of intact viral DNA within CD4+ T cells was about 40% lower than with ART alone, while the number of infected cells circulating in the blood was approximately 79% lower. Importantly, the reduction persisted for nearly nine months after venetoclax was discontinued and was also observed in lymph nodes.

The findings suggest that intervening as ART begins—when the long-term viral reservoir is still becoming established—could make infected cells easier to eliminate. A short course of treatment might therefore have lasting effects without requiring continuous venetoclax use.

Venetoclax temporarily lowered several immune-cell populations, but counts subsequently approached those seen with ART alone. The study did not stop ART, so it remains unknown whether reducing the reservoir would delay viral rebound or allow treatment-free control. Two early-stage clinical trials are now evaluating venetoclax in people with HIV, including those starting ART and those already virally suppressed.

“Eliminating the viral reservoir is a priority in the pursuit of a cure for HIV,” said senior author Mirko Paiardini, PhD. “Our study, however, offers hope for accelerating the timeline to cure by using an approved medication.”

Source: Wiche Salinas TR, et al. (2026 Sep 3) Nat Microbiol. BCL-2 inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques