The AIDS Clinical Trials Group (ACTG) presented promising phase 2 trial results at the 2025 Conference on Retroviruses and Opportunistic Infections, demonstrating that letermovir, a drug approved for CMV prevention in transplant recipients, may improve immune function and physical health in people living with HIV who have asymptomatic CMV. Despite effective antiretroviral therapy (ART), CMV, prevalent in people with HIV, can still impact immune function and contribute to inflammation. The study, A5383, suggests treating asymptomatic CMV could be a novel approach to improving long-term health outcomes for this population.
This research is crucial because it addresses a persistent challenge in HIV care: the accelerated aging and premature mortality observed in individuals with HIV despite ART. While ART effectively suppresses HIV, it doesn’t fully address the long-term effects of chronic inflammation, which are potentially exacerbated by persistent CMV infection. This study suggests a pathway to mitigate these effects, improving both immune function and physical health, potentially leading to a longer, healthier lifespan for people with HIV.
The A5383 study was a randomized, open-label trial where participants received either letermovir or no CMV treatment. Treatment with letermovir significantly increased CD4 counts, particularly in women and individuals with persistently low CD4 T cells. Improvements were also observed in the CD4/CD8 ratio, a marker of immune system dysregulation, and in physical function tests. Notably, the improvements in physical function correlated strongly with the immunologic improvement.
These findings suggest a new avenue for improving the health and well-being of people living with HIV. If confirmed by larger studies, letermovir treatment for asymptomatic CMV could become a standard of care, offering a much-needed strategy to combat the long-term health challenges faced by this population. Further research could explore the potential benefits of this approach in other populations affected by CMV, such as the elderly and transplant recipients.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
