Antiretroviral therapy (ART) has transformed HIV from a life-threatening infection into a manageable chronic condition. But even when ART can suppress the virus to undetectable levels, HIV can persist in long-lived infected cells known as the viral reservoir. If treatment stops, these cells can allow the virus to rebound.
New research from Emory National Biomedical Research Center suggests venetoclax, medication already approved to treat certain cancers may help reduce the persistent viral reservoir that makes HIV difficult to cure. In a study published in Nature Microbiology, researchers demonstrated for the first time in a nonhuman primate model venetoclax can reduce levels of the simian immunodeficiency virus (SIV) reservoir when used alongside ART.
How Venetoclax May Target the HIV Viral Reservoir
Venetoclax, a medication approved to treat certain cancers, works by blocking BCL-2, a protein that helps regulate whether cells live or die and can promote the survival of cancer cells. Researchers have found BCL-2 can similarly help HIV-infected cells survive, allowing them to become part of the viral reservoir.
Mirko Paiardini, Ph.D., chief of the Microbiology and Immunology Division at the Emory National Biomedical Research Center (ENBRC) and senior author of the study, said eliminating the viral reservoir is a priority in the pursuit of an HIV cure. Because venetoclax is already an approved medication, Paiardini said the findings offer hope for accelerating the timeline toward a cure.
What Did Researchers Learn From the SIV Study?
Researchers studied whether adding venetoclax to ART could reduce the persistent viral reservoir in rhesus macaques infected with SIV, the virus commonly used to model HIV infection in nonhuman primates. Beginning 14 days after infection, the animals received ART alone or ART in combination with venetoclax. One treatment group also received a CD8α-depleting antibody.
After 10 days of venetoclax treatment, researchers observed a more rapid reduction in SIV-infected CD4+ T cells compared with ART alone. Importantly, the intact SIV reservoir remained lower for months after venetoclax treatment ended while ART continued. The findings signal blocking BCL-2 may help reduce the persistent viral reservoir in a living system.
What Comes Next for Venetoclax and HIV Research?
The study provides evidence supporting further study of BCL-2 inhibition as one component of future HIV cure strategies. Paiardini’s team is now studying whether administering venetoclax for longer periods could have a greater effect on the viral reservoir and investigating how some infected cells survive despite BCL-2 being blocked. Clinical studies are also evaluating venetoclax in people living with HIV.
Together, these next steps could help researchers build on this early progress and accelerate the search for strategies that can eliminate persistent HIV reservoirs, bringing the field closer to the long-term goal of a cure.
Frequently Asked Questions About HIV Reservoir Research
What is HIV?
HIV, or human immunodeficiency virus, attacks cells in the immune system, particularly CD4+ T cells. Without treatment, HIV can weaken the immune system and progress to AIDS. Antiretroviral therapy can suppress the virus and help people with HIV live long, healthy lives, but it does not eliminate the persistent viral reservoir that remains in the body.
What is the HIV viral reservoir?
The HIV viral reservoir is a population of infected cells that can persist even when ART has suppressed the virus. These long-lived cells are a major challenge researchers must address in the pursuit of an HIV cure.
What is venetoclax?
Venetoclax is a medication approved to treat certain cancers. It blocks BCL-2, a protein that helps some cells survive. Researchers are studying whether blocking BCL-2 can also help eliminate HIV-infected cells that contribute to the viral reservoir.
Is venetoclax currently used to treat HIV?
No. Venetoclax is approved to treat certain cancers, not HIV. Researchers are studying whether it can safely help reduce the HIV viral reservoir when used alongside ART, but additional clinical research is needed.
Funding
The research reported in this release is supported in part by the by the Emory National Biomedical Research Center’s base grant from the NIH Office of the Director, other NIH institutes and the Center for AIDS Research. The publication contents are those of the authors and do not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. government. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Grant amounts (direct + indirect)
NIH/OD
P51OD011132, $10,751,414 (2026)
U42 PDP11023, $1,531,512 (2026)
NIH and NIAID, NHLBI, NIDDK, NINDS and NIDA
UM1AI164562 Martin Delaney Collaboratory program, ERASE-HIV, $4,657,427 (2026)
NIH and National Cancer Institute
Contract No. 75N91019D00024, $1,685,930 (2024)
NIAID
AI110173, $752,862 (2024)
R56AI183801, $682,446 (2024)
CFAR
P30AI050409, $1,488,520 (2026)
Note: The amounts listed above are for the full grants. Only a portion of each grant supported the research reported in this news release.
DOL: 10.1038/s41564-026-02464-7
