Common drug may help HIV medicines work faster and reduce inflammation

JUPITER, Fla. — An FDA‑approved medication called spironolactone, often prescribed as a diuretic, or water pill, for heart and blood pressure conditions, may be a useful add‑on to the standard HIV treatment, according to new research from the Valente lab at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology.

Viruses spread by hijacking cells and using their gene transcription machinery to make new viral copies. Today’s HIV medicines keep the virus under control but are not a cure. If treatment stops, HIV can return from hidden reservoirs, so a more durable, long-lasting treatment is needed. In the new study, researchers used HIV-infected mice with human immune cells, and added a long‑acting form of spironolactone to the standard, first‑line antiretroviral therapy.

The combined medications made the amount of virus in the bloodstream drop more quickly than the standard HIV treatment alone. It also reduced signs of inflammation in tissue, without lowering immune cell counts or changing the amount of HIV’s genetic material that remains hidden inside cells, said co-corresponding author Susana T. Valente, Ph.D., who chairs the immunology and microbiology department at The Wertheim UF Scripps Institute.

“December 1 was World AIDS Day, so it was very meaningful to us that this research was published this week,” Valente said. “People living with HIV have extraordinarily effective control with current antiretroviral therapy, but it doesn’t eliminate the long‑lived viral reservoir, or fully silence residual viral transcription. This reservoir is linked to chronic inflammation and HIV‑related comorbidities, so we’re committed to doing more to help people living with HIV infection.”

The new study was published online on Sunday, Nov. 30, in the journal Emerging Microbes & Infections. The researchers found that adding spironolactone led to a significant 4.4‑fold reduction in cell‑associated HIV RNA across the body and broadly lowered activity in genes linked to inflammation. The amount of proviral DNA, the HIV genetic material that can persist in the body, did not change, suggesting spironolactone helped quiet viral activity rather than remove infected cells, Valente said.

Valente said her ultimate goal is to enable people infected with HIV to achieve durable viral suppression by finding a safe, affordable add‑on therapy to “quiet” the virus. She calls the approach a “block‑and‑lock” strategy, and believes it could improve long‑term health of people with HIV.

“By adding a transcriptional inhibitor like spironolactone to antiretroviral therapy, we saw faster plasma viral decay and marked reductions in HIV RNA and inflammatory gene expression in tissues, suggesting a practical path to both hasten suppression and mitigate inflammation,” she said.

The medication has a longstanding clinical safety record. It is prescribed as a modulator of the steroid hormone aldosterone, which regulates sodium and water balance in cells. In the study, spironolactone, via an off-target mechanism, reduced viral gene expression, accelerating the virus’s entry into latency.

Even with today’s standard antiretroviral therapy, small amounts of viral activity can continue and are associated with inflammation and health complication, Valente said. Safe, affordable add‑on therapies that further “quiet” the virus could improve long‑term health, she said.

The next step in the research is to conduct additional preclinical studies, to refine dosing and timing. The researchers also plan to test spironolactone in combinations with other drugs that suppress viral activity, evaluating durability, safety, and drug levels as they consider future clinical feasibility studies.

“These findings support exploring transcriptional inhibitors like spironolactone as adjuncts to ART to hasten suppression and mitigate chronic inflammation,” Valente said.

The study, “Combining spironolactone to antiretroviral therapy accelerates HIV decay in humanized mice,” appears in Emerging Microbes & Infections and is open access. Other authors include Michael D. Cameron, Ph.D., and Luisa P. Mori of The Wertheim UF Scripps Institute, as well as co-corresponding author J. Victor Garcia, Ph.D., Lijun Ling, Andrew Soper, Wenbo Yao, Rae Ann Spagnuolo, Nurjahan Begum, Martina Kovarova and Angela Wahl of the University of North Carolina Chapel Hill and University of Alabama Centers for AIDS Research programs.

The research was funded by the National Institutes of Health National Institute of Allergy and Infectious Disease grants 5R01AI097012‑11, R01AI177327 and R01AI140799, with support from the Collaboratory of AIDS Researchers for Eradication (CARE) and HIV Obstruction by Programmed Epigenetics (HOPE) two Martin Delaney Collaboratories (1UM1AI126619 and UM1 AI164559), and from the UNC Chapel Hill and University of Alabama Centers for AIDS Research (CFAR) programs P30AI050410 and P30AI027767.