Researchers at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology have found that spironolactone, a diuretic commonly used to treat heart and blood pressure conditions, may be an effective addition to standard HIV therapy. The study involved treating HIV-infected mice with human immune cells using both first-line antiretroviral therapy and a long-acting form of spironolactone.
The research showed that the combination led to a faster reduction in the amount of virus present in the bloodstream compared to antiretroviral therapy alone. Additionally, signs of inflammation in tissues were reduced without affecting immune cell counts or changing the level of hidden HIV genetic material within cells, according to Susana T. Valente, Ph.D., co-corresponding author and chair of immunology and microbiology 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 described their approach as "block-and-lock": blocking the virus's ability to copy its genes and locking it into a dormant state.
The findings, published on November 30 in Emerging Microbes & Infections, indicate that adding spironolactone resulted in a significant 4.4-fold reduction in HIV RNA inside cells throughout the body and decreased activity in genes related to inflammation. However, there was no change in proviral DNA levels—the genetic material from HIV that can persist—suggesting spironolactone helps reduce viral activity rather than eliminating infected cells.
Spironolactone has been used safely for many years by blocking aldosterone—a hormone responsible for regulating salt and water balance—but appeared here also to suppress HIV gene activity through another mechanism.
Valente noted that even with current therapies, some ongoing viral activity remains associated with inflammation and health complications. She said affordable add-on treatments like spironolactone could improve long-term outcomes for those living 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.
Future steps include further preclinical studies on dosing and timing as well as testing combinations with other drugs aimed at suppressing viral activity before moving toward clinical trials evaluating safety and efficacy.
"These findings support exploring transcriptional inhibitors like spironolactone as adjuncts to antiretroviral therapy to hasten suppression and mitigate chronic inflammation," Valente said.
