Lenacapavir, from Gilead Sciences, is an investigational antiretroviral medicine called a capsid inhibitor that targets the cone-shaped shell of the virus and proteins important to viral reproduction. Previous research showed that lenacapavir interrupts multiple stages in the viral life cycle, helping to suppress the virus. NewYork-Presbyterian Queens was one of 42 investigational sites for lenacapavir around the world.
“Despite significant advances in antiretroviral treatments that have helped many people with HIV suppress the virus, there are still patients with treatment failures due to viral resistance or unacceptable side effects,” said Dr. Segal-Maurer. “These patients no longer have viral suppression and require treatment options that can be complex and difficult to adhere to, leading to further drug resistance. These challenges underscore the importance of new treatment options for people living with multi-drug resistant HIV infection.”
The phase II/III CAPELLA trial included 72 people living with HIV with a median age of 52, 75% of whom were men. Individuals were eligible for the study if they were age 12 and older, were currently on a failing drug regimen, and had developed resistance to at least two drugs from four main classes of antiretroviral medications (46% of patients in the study had resistance to all four major classes of antiretroviral medications). Half of the trial participants were randomized to receive oral lenacapavir or a placebo along with their existing medication regimen for 14 days.
The remaining 36 participants started taking lenacapavir pills at the beginning of the trial on top of a regimen of HIV medications designed to maximize effectiveness for these heavily treatment-experienced people. After 14 days on the oral drug, they, too, switched to the subcutaneous injections.
At the end of the lead-in period, 88% of participants receiving lenacapavir saw a significant drop in their viral level, compared with just 17% of those on the placebo. Trial participants randomized to receive lenacapavir also experienced an increase in white blood cells called CD4 T cells, critical to fighting the infection. Overall, the percentage of people with profoundly low CD4 T cells decreased from 24% to 0%. No one dropped out of the study as a result of drug-related side effects, according to Dr. Segal-Maurer.
“The significance of the trial’s findings is profound. We’ve come a long way,” said Dr. Segal-Maurer, who has witnessed the evolution of HIV treatment over the decades, starting at the beginning of the AIDS epidemic. “I was in medical school in the early to mid-eighties when the average lifespan between diagnosis and death was anywhere from weeks to months. We’ve gone from many pills multiple times a day to one pill a day to possibly even less. Now we’re in a place where if a patient can engage in care and take their medicine, they have an excellent chance for improved outcomes and a long lifespan.”
Dr. Sorana Segal-Maurer is a paid consultant for Gilead Sciences.
Sorana Segal-Maurer, M.D., is director of the Dr. James J. Rahal, Jr. Infectious Diseases Division at NewYork-Presbyterian Queens and professor of clinical medicine at Weill Cornell Medicine. She is the site principal investigator for a number of studies evaluating new investigational HIV antiretroviral therapies.