Imagine if a common water pill could change the way we treat HIV — sounds surprising, right? But new research suggests it might. Scientists at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, led by the Valente lab, have discovered that spironolactone, an FDA-approved medication usually prescribed as a diuretic for heart and blood pressure issues, could serve as a powerful addition to standard HIV therapy.
HIV spreads by taking over human cells and using their machinery to make more copies of itself. While current antiretroviral treatments are highly effective at controlling the virus, they are not a cure. If treatment is paused, HIV can resurface from hidden reservoirs inside the body, which is why researchers are constantly searching for more lasting strategies. In this recent study, the team treated HIV-infected mice, implanted with human immune cells, using standard antiretroviral therapy along with a long-acting version of spironolactone.
The results were striking: the combination therapy reduced the amount of virus in the bloodstream more quickly than antiretroviral therapy alone. It also decreased signs of inflammation in various tissues, without lowering immune cell counts or altering the hidden HIV genetic material inside cells. Susana T. Valente, Ph.D., co-corresponding author and chair of the immunology and microbiology department at the Wertheim UF Scripps Institute, explained that the medication seems to suppress viral activity without eradicating infected cells.
"Publishing this research around World AIDS Day was very meaningful for us," Valente said. "Current antiretroviral therapy provides extraordinary control, but it doesn’t eliminate the long-lived viral reservoir or completely shut down residual viral gene activity. This reservoir contributes to chronic inflammation and HIV-related health issues, so our goal is to find ways to further support people living with HIV." Valente described the approach as "block-and-lock": preventing the virus from replicating its genes and locking it into a long-term dormant state.
Published online on November 30 in Emerging Microbes & Infections, the study showed that adding spironolactone led to a 4.4-fold decrease in HIV RNA within cells across the body and significantly reduced the activity of inflammation-related genes. However, the amount of proviral DNA—the portion of HIV's genetic code that can persist in the body—remained unchanged. This suggests that spironolactone’s role is to quiet viral activity rather than eliminate infected cells.
Spironolactone is well-known for its safety profile and works by blocking aldosterone, a hormone that regulates salt and water in the body. Interestingly, in this study, it also appeared to suppress HIV gene activity through a separate mechanism, helping the virus enter a dormant state more quickly.
Even with today’s antiretroviral therapy, small amounts of viral activity can persist, causing inflammation and increasing the risk of long-term health complications. Valente emphasized that safe and affordable add-on therapies that further calm the virus could enhance the long-term well-being of patients living with HIV.
"By introducing a transcriptional inhibitor like spironolactone alongside antiretroviral therapy, we observed faster reduction of virus in the blood and substantial decreases in HIV RNA and inflammatory gene expression in tissues. This points to a promising approach for accelerating viral suppression while reducing inflammation," she said.
The next step involves additional preclinical studies to optimize dosing and timing. The team also plans to test spironolactone with other drugs that suppress viral activity, assessing long-term safety, drug levels, and overall effectiveness before moving into clinical trials.
"These findings suggest that exploring transcriptional inhibitors like spironolactone as adjuncts to antiretroviral therapy could be a valuable strategy to speed up viral suppression and reduce chronic inflammation," Valente concluded.
Source:
Emerging Microbes & Infections, November 30, 2025.
