ACTG Presents Study at CROI Demonstrating Potential of CMV-specific Antiviral Inhibitor to Improve Aging-Related Outcomes among People Living with HIV and CMV (Cytomegalovirus)

/EIN News/ -- LOS ANGELES, March 12, 2025 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today presented promising findings from a study exploring how treating asymptomatic cytomegalovirus (CMV) in people living with HIV may improve immune function and physical health. The results from study A5383 were shared as the oral abstract, “Asymptomatic CMV Suppression with Letermovir Improves Immunologic and Functional Aging-related Outcomes in Treated HIV” at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, California.

CMV is a common virus carried by most adults and 95 percent of people living with HIV. Before the introduction of effective antiretroviral therapy (ART), CMV often led to life-threatening conditions in the eyes, brain, and gut in individuals with advanced HIV. While ART has dramatically reduced these cases by strengthening the immune system, CMV can still affect immune function and contribute to inflammation, even in the absence of noticeable symptoms. Letermovir is a medication that has been approved by the Food and Drug Administration (FDA) to prevent CMV infection and disease in people who have received transplants.

“This is an important finding and ACTG is especially excited because there are currently no interventions that improve immune recovery and functional status in people living with HIV who are taking effective antiretroviral therapy,” said ACTG Chair Joseph J. Eron, M.D., University of North Carolina. “Larger studies are needed to confirm these results; if they do, this intervention could represent a significant breakthrough in HIV and aging research.”

A5383 study was a phase 2, randomized, open-label trial designed to assess whether letermovir could reduce inflammation and improve immune recovery in people living with HIV on ART who were CMV-positive but without detectable HIV in their blood. Participants were randomly assigned to either receive letermovir daily for 48 weeks or no CMV treatment. Although an early analysis initially showed a temporary increase in inflammatory markers, continued treatment led to sustained reductions in inflammation and improvements in immune and physical function.

Today’s presentation demonstrated that treatment with letermovir led to a significant increase in CD4 counts, with the most pronounced benefits seen in women and individuals whose CD4 T cells remained persistently low. Additionally, those receiving letermovir showed improvements in their CD4/CD8 ratio (a marker of immune system dysregulation that is associated with heart disease, cancer, and mortality in people living with HIV and in elderly populations) and physical function, including an enhancement in chair rise performance (a marker of leg strength and mobility). In addition, improvements in physical function with letermovir correlated strongly with the immunologic improvement observed, suggesting that these beneficial effects were closely linked.

“Our team has been working for the last 20 years to address the accentuated aging and premature mortality seen in people living with HIV despite modern treatment,” said Sara Gianella, M.D., Co-Chair of study A5383, University of California San Diego. “We are particularly intrigued to see that it appears that immunologic improvements were greater in women, because in the setting of HIV, women have more inflammation than men, and a greater ‘life expectancy gap’ compared to the general population. These data may also have important implications for the role of CMV in other settings outside HIV, like the elderly and transplant recipients, where CMV has been hypothesized to play a role in long-term health outcomes.”

A5383 was led by Dr. Gianella and Peter Hunt, M.D., University of California San Francisco (Protocol Chair). ACTG is led by Dr. Eron and Rajesh T. Gandhi, M.D., Massachusetts General Hospital and Harvard Medical School (ACTG Vice-Chair). It is sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. Study drugs were supplied by Merck & Co., Inc, Rahway, N.J., USA.

About ACTG
ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.

Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH.

Media Contact:
Rachel Reiss, ACTG
RLReiss@mednet.ucla.edu