Common water pill may help HIV medicines work faster and reduce inflammation, early study suggests

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 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 more durable, long-lasting approaches are needed. In the new study, researchers treated HIV-infected mice with human immune cells with first‑line antiretroviral therapy plus a long‑acting form of spironolactone.

The combination made the amount of virus in the bloodstream drop faster than antiretroviral therapy alone. It also reduced signs of inflammation in tissues, without lowering immune cell counts or changing the amount of HIV genetic material that stays 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.” She describes the team’s approach as “block-and-lock”: block the virus’s ability to copy its genes and lock in into a long-lasting dormant state.

The study, published online Nov. 30 in Emerging Microbes & Infections, found that adding spironolactone led to a significant 4.4‑fold reduction in HIV RNA inside cells 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.

Spironolactone has a long clinical safety record. It works by blocking aldosterone, a hormone that helps the body regulate salt and water. In this study, it also appeared to quiet HIV’s gene activity through a separate effect, helping the virus enter a dormant state faster.

Even on 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.

“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 next step is additional preclinical studies to refine dosing and timing. The team also plans to test spironolactone in combination with other drugs that suppress viral activity, evaluating durability, safety, and drug levels as they consider future clinical efficacy studies.

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