Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection
Sorana Segal‐Maurer, Edwin DeJesus, Hans‐Jürgen Stellbrink, Antonella Castagna, Gary Richmond, Gary Sinclair, Krittaecho Siripassorn, Peter Ruane, Mezgebe Berhe, Hui Wang, Nicolas Margot, Hadas Dvory‐Sobol, Robert H. Hyland, Diana M. Brainard, Martin S. Rhee, Jared M. Baeten, Jean‐Michel Molina
Abstract
BACKGROUND: Patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection have limited treatment options. Lenacapavir is a first-in-class capsid inhibitor that showed substantial antiviral activity in a phase 1b study. METHODS: copies per milliliter in the viral load by day 15; a key secondary end point was a viral load of less than 50 copies per milliliter at week 26. RESULTS: copies per milliliter in the viral load by day 15 was observed in 21 of 24 patients (88%) in the lenacapavir group and in 2 of 12 patients (17%) in the placebo group (absolute difference, 71 percentage points; 95% confidence interval, 35 to 90). At week 26, a viral load of less than 50 copies per milliliter was reported in 81% of the patients in cohort 1 and in 83% in cohort 2, with a least-squares mean increase in the CD4+ count of 75 and 104 cells per cubic millimeter, respectively. No serious adverse events related to lenacapavir were identified. In both cohorts, lenacapavir-related capsid substitutions that were associated with decreased susceptibility developed in 8 patients during the maintenance period (6 with M66I substitutions). CONCLUSIONS: In patients with multidrug-resistant HIV-1 infection, those who received lenacapavir had a greater reduction from baseline in viral load than those who received placebo. (Funded by Gilead Sciences; CAPELLA ClinicalTrials.gov number, NCT04150068.).