Subcutaneous Lenacapavir Effective for Patients With Multidrug-Resistant HIV

Among heavily treatment-experienced patients with multidrug-resistant HIV infection, subcutaneous lenacapavir in combination with an optimized background regimen was well tolerated and found to be associated with high rates of sustained virologic suppression for up to 52 weeks. These study results were presented at IDWeek 2022, held from October 19 to 23, in Washington, DC.

Lenacapavir is a potent first-in-class inhibitor of HIV-1 capsid function.

Researchers assessed the efficacy of lenacapavir against multidrug-resistant HIV infection among heavily treatment-experienced patients enrolled in an ongoing phase 2/3 trial. Patients (n=36) were randomly assigned in a 2:1 fashion to receive either oral lenacapavir or placebo in addition to their failing regimen. At day 15 after enrollment, subcutaneous lenacapavir (927 mg) was administered every 6 months among patients in the treatment group. For patients in the placebo group, oral lenacapavir followed by subcutaneous doses every 6 months were initiated at day 15 after enrollment. Patients in both cohorts also received an optimized background regimen starting at day 15.

A second nonrandomized cohort of 36 patients who received an optimized background regimen concurrently with oral lenacapavir followed by subcutaneous administration were included in the analysis. Safety and efficacy outcomes through week 52 were reported from both the randomized and nonrandomized patient cohorts.

Among a total of 72 patients included in the analysis, the median age was 52 years, 25% were women, and 38% were Black. In addition, 64% of patients had CD4 counts of less than 200 cells/µL, 46% had resistance to the 4 major HIV-1 antiretroviral drug classes, and 53% received an optimized background regimen with 1 or no fully active agents.

At week 52, 78% of the patients achieved a viral load of less than 50 cells/mL and 82% achieved a viral load of less than 200 cells/mL.

The median increase in CD4 counts among the patients was 84 cells/µL between the first to the third quarter. At week 52, the percentage of patients who had CD4 counts of 200 cells/µL or greater increased from 36% at baseline to 68%.

Two patients developed emergent lenacapavir resistance, and 8 had previously reported resistance. Of these 10 patients, subsequent suppression was observed in 4.

During a median follow-up period of 73 (range, 13-111) weeks, 1 patient discontinued treatment with lenacapavir due to grade 1 nodule at the injection site. Swelling was the most common type of injection site reaction, occurring in 28% and 17% of patients after receipt of the first and second subcutaneous doses of lenacapavir, respectively. With the exclusion of injection site reactions, diarrhea (14%) and nausea (14%) were the most commonly reported adverse events.

“These results support the potential role for LEN [lenacapavir] for treatment of multi-drug resistant HIV-1 infection,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.