LOS ANGELES, March 12, 2025 — The AIDS Clinical Trials Group (ACTG), a leading global network devoted to HIV research, has unveiled groundbreaking insights from a new study suggesting that treating cytomegalovirus (CMV) in people living with HIV can significantly improve their immune function and overall physical health. The results were shared during an oral presentation titled “Asymptomatic CMV Suppression with Letermovir Improves Immunologic and Functional Aging-related Outcomes in Treated HIV” at the prestigious 2025 Conference on Retroviruses and Opportunistic Infections (CROI) held in San Francisco.

CMV is an opportunistic virus that often goes unnoticed in most adults, yet it affects 95% of individuals living with HIV. Historically, before the advent of effective antiretroviral therapy (ART), CMV was a leading cause of severe health issues in people with advanced HIV, affecting vital organs such as the eyes and brain. While ART has greatly curtailed these severe manifestations, CMV can still negatively impact immune health and contribute to systemic inflammation, even when symptoms are not present.

Letermovir, an FDA-approved antiviral intended primarily for transplant recipients, has shown potential in preventing CMV infection. “This is an important finding, as currently there are no interventions designed to enhance immune recovery in people with HIV who are undergoing ART,” remarked ACTG Chair Joseph J. Eron, M.D., from the University of North Carolina. “If further studies back these findings, this could potentially transform the landscape of HIV care and aging research.”

The study, designated A5383, was a phase 2, randomized, open-label trial that assessed letermovir’s impact on individuals living with HIV on ART who tested positive for CMV but had undetectable levels of HIV. Participants were divided into two groups: one receiving letermovir daily for 48 weeks and the other foregoing any CMV treatment. Although initial analyses indicated a temporary spike in inflammatory markers, prolonged treatment revealed sustained reductions in inflammation and significant improvements in both immune and physical function.

Key outcomes of the study indicated that letermovir treatment resulted in a notable increase in CD4 cell counts, particularly benefiting women and individuals with persistently low CD4 T cell counts. Furthermore, improvements in the CD4/CD8 ratio—a critical measure linked to immune dysfunction—were observed, alongside enhanced physical abilities, such as improved chair rise performance, highlighting increased leg strength and mobility. The correlation between physical improvements and immune enhancements suggests a compelling link between these health aspects.

Dr. Sara Gianella, Co-Chair of the A5383 study from the University of California San Diego, noted, “Our team has dedicated two decades to understanding the accelerated aging and premature mortality experienced by individuals living with HIV, even with advancements in treatment. We find it particularly intriguing that immunological benefits were more pronounced in women, who often experience more inflammation and a greater life expectancy gap compared to men and the general population.”

The implications of this research extend beyond just the realm of HIV. The role of CMV in aging and chronic health outcomes in other populations, such as the elderly and organ transplant recipients, is increasingly being recognized, which could further shape public health strategies.

Led by Dr. Gianella and Dr. Peter Hunt from the University of California San Francisco, the A5383 trial is backed by funding from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID). This promising development sets the stage for larger trials to confirm these results, possibly heralding a new era of care for people living with HIV.

As researchers closely monitor these findings, the hope remains that innovative approaches can significantly enhance the health and longevity of individuals battling HIV and its complications. Stay tuned for more updates on this evolving story, as it reflects not only advancements in HIV care but also offers insights into the broader impacts of viral infections on aging and health outcomes.