Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection
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.).