A common water pill, spironolactone, may enhance HIV treatment, according to new research from the Valente lab at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology. This medication, typically prescribed for heart and blood pressure issues, could be a valuable addition to standard HIV therapy, offering a more durable and long-lasting solution.
HIV spreads by hijacking cells and using their gene transcription machinery to replicate. Current HIV medications effectively control the virus but are not a cure. Discontinuing treatment can lead to the virus reemerging from hidden reservoirs, necessitating more robust and prolonged treatment approaches. In the study, researchers treated HIV-infected mice with human immune cells using first-line antiretroviral therapy and a long-acting form of spironolactone.
The combination resulted in a faster decrease in viral levels in the bloodstream compared to antiretroviral therapy alone. It also reduced inflammation in tissues without impacting immune cell counts or altering the amount of HIV genetic material in cells, as explained by co-corresponding author Susana T. Valente, Ph.D., who chairs the immunology and microbiology department at The Wertheim UF Scripps Institute. The team's approach, dubbed 'block-and-lock,' aims to prevent the virus from replicating and maintain it in a long-term dormant state.
The study, published in Emerging Microbes & Infections, revealed that adding spironolactone led to a significant 4.4-fold reduction in HIV RNA within cells throughout the body and generally decreased gene activity linked to inflammation. The amount of proviral DNA, the HIV genetic material, remained unchanged, indicating that spironolactone helped suppress viral activity rather than eliminate infected cells, according to Valente.
Spironolactone has a well-established safety record in clinical use. It functions by blocking aldosterone, a hormone that regulates salt and water balance in the body. In this study, it also appeared to suppress HIV gene activity through an additional mechanism, facilitating a quicker transition to a dormant state.
Safe, affordable adjunct therapies that further suppress the virus could enhance long-term health, as even on current antiretroviral therapy, small amounts of viral activity persist, linked to inflammation and health complications, according to Valente. By incorporating a transcriptional inhibitor like spironolactone into antiretroviral therapy, the research team observed accelerated plasma viral decay and significant reductions in HIV RNA and inflammatory gene expression in tissues, suggesting a practical approach to hastening suppression and mitigating inflammation.
The next phase involves additional preclinical studies to optimize dosing and timing. The team also plans to test spironolactone in conjunction with other drugs that suppress viral activity, assessing durability, safety, and drug levels, with a view to future clinical efficacy studies.
'These findings support the exploration of transcriptional inhibitors like spironolactone as adjuncts to antiretroviral therapy to hasten suppression and mitigate chronic inflammation,' Valente said.
