The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the initiation of A5383, a clinical trial evaluating whether the anti- cytomegalovirus (CMV) drug letermovir reduces inflammation when given to people who have well-controlled HIV and CMV without symptoms.
Approximately 90% of people living with HIV also have CMV and there is strong evidence that CMV is associated with chronic inflammation and possibly with end organ disease, including cardiovascular disease, neurological complications, and metabolic disease. Letermovir is a CMV DNA terminase complex inhibitor that is FDA-approved to prevent severe CMV disease in adults with asymptomatic CMV who are receiving allogeneic hematopoietic stem cell transplants (generally for the treatment of blood cancer). Because of letermovir’s utility and safety profile among these individuals, researchers hypothesize that letermovir may also reduce the amount of CMV and consequently decrease inflammation in people living with HIV.
“Because it is nearly ubiquitous among people living with HIV, CMV remains an important research focus as we seek to improve quality of life among people who are aging with HIV,” said ACTG chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “This study is particularly important because it will determine whether suppressing asymptomatic CMV replication will decrease systemic inflammation.”
A5383 is a phase 2, randomized, open-label, controlled, multicenter trial evaluating the anti-inflammatory efficacy of letermovir among adults age 40 and older, whose HIV is virally suppressed while on antiretroviral therapy (ART) and whose CMV is asymptomatic. Half of participants (n=90) will receive 480 mg of letermovir once daily (administered orally as either one or two tablets) and half will not receive any anti-CMV therapy. Participants will be followed for 60 weeks, including 48 weeks taking letermovir for participants in the active group and 12 weeks of post-treatment follow-up. At least one-third of participants will be cisgender or transgender women and half will have CD4+ T cell counts <350 cells/mm3.
“Based on preliminary data, we believe this intervention may be particularly helpful for several groups of people: those who continue to have low CD4 counts despite viral suppression, individuals at highest risk for morbidity and mortality and thus most in need of new interventions, and women, who tend to be underrepresented in most treatment studies,” said protocol co-chair Sara Gianella, M.D., University of California, San Diego. “We are pleased that this study has been designed in a way that features a dedicated effort to recruit these individuals.”
A5383 is led by Dr. Gianella and Peter Hunt, M.D., University of California at San Francisco (study chair). It is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Study drugs are supplied by Merck & Co., Inc.