Trial to Evaluate Anti-Cytomegalovirus Drug in Treating Inflammation in Patients With HIV

Letermovir has been approved by the FDA to prevent severe CMV in patients who are asymptomatic and undergoing allogeneic hematopoietic stem cell transplants.

A phase 2, randomized, open-label, controlled, multicenter trial will evaluate the efficacy of an anti-cytomegalovirus (CMV) drug in treating inflammation in patients with well-controlled HIV.

The A5383 trial, initiated by The AIDS Clinical Trials Group (ACTG), will analyze the efficacy of letermovir, a CMV DNA terminase complex inhibitor, in lowering inflammation in patients who have well-controlled HIV and CMV without symptoms. The ACTG noted that approximately 90% of patients with HIV also have CMV, adding that evidence supports an association between CMV and chronic inflammation, as well as a potential association with end organ disease, such as cardiovascular disease, neurological complications, and metabolic disease.

Letermovir has been approved by the FDA to prevent severe CMV in patients with asymptomatic CMV who are undergoing allogeneic hematopoietic stem cell transplants—generally for the treatment of blood cancer.

ACTG investigators said that letermovir may be able to decrease the amount of CMV and inflammation in people living with HIV based on its existing utility and safety profile in this patient population.

“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,” ACTG chair Judith Currier, MD, MSc, University of California, Los Angeles, said in a press release. “This study is particularly important because it will determine whether suppressing asymptomatic CMV replication will decrease systemic inflammation.”

A5383 will analyze the anti-inflammatory efficacy of letermovir in adults 40 years of age and older with HIV that is virally suppressed with antiretroviral therapy and whose CMV is asymptomatic.

Half of the patients (n=90) will be administered 480 mg of letermovir once daily orally as either 1 or 2 tablets, whereas the control group will not receive any anti-CMV therapy. The patients will be followed for 60 weeks, with 48 weeks of letermovir use in patients in the active group and 12 weeks of post-treatment follow-up.

The study will include at least one-third of patients who are 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,” protocol co-chair Sara Gianella, MD, University of California, San Diego, said in a press release. “We are pleased that this study has been designed in a way that features a dedicated effort to recruit these individuals.”

The trial will be led by Dr. Gianella and Peter Hunt, MD, University of California at San Francisco and is funded by the National Institute of Allergy and Infectious Diseases.

Reference

ACTG launches A5383, clinical trial evaluating potential immunologic benefits of treating asymptomatic CMV in people living with HIV. Aids Clinical Trials Group. News release. https://www.eurekalert.org/news-releases/950436. April 25, 2022.