Long-acting lenacapavir helps maintain viral suppression in many multidrug-resistant patients, two-year data show

For people who are heavily HIV treatment-experienced with multidrug resistance, an extension of an ongoing trial finds encouraging two-year viral suppression rates among people who added injectable lenacapavir to their background regimen.

About This Study

“Efficacy and Safety of Long-Acting Subcutaneous Lenacapavir in Heavily Treatment-Experienced People with Multi-Drug Resistant HIV-1: Week 104 Results of a Phase 2/3 Trial” was published online on Aug. 29, 2024, in Clinical Infectious Diseases. The lead author is Onyema Ogbuagu, MBBCh, FACP, FIDSA, of the Yale University School of Medicine in New Haven, Connecticut. The study was funded by Gilead Sciences, the manufacturer of the study drug, and several study authors are company employees.

Key Research Findings

Researchers investigated the long-acting antiretroviral lenacapavir in 72 people whose HIV was resistant to medications in three of the four main drug classes. Screening took place between 2019 and 2021 in 11 different countries. This is an open-label extension of the international CAPELLA study that compared the study drug to placebo at week 52. Participants in the current study were on individualized background regimens to which subcutaneous injections of the study drug every 26 weeks were added.

Median participant age was 52 years and 75% of participants were men, 41% of participants were white, 38% Black, and 21% Asian. At baseline, mean viral load was 4.17 log₁₀ copies/mL and mean CD4 count was 210 cells/µL. Almost everyone’s virus was resistant to the older drug classes, and the HIV of 46% of participants was resistant to drugs in all four drug classes.

By week 104, CD4 counts increased a mean 122 cells/µL among the 55 participants with available data. Viral loads decreased to <50 copies/mL in 82% of the 54 participants with available data, and to >50 but <200 copies/mL in one participant.

Fourteen participants developed resistance against the study drug, with seven participants re-suppressing after changes to their background regimens. AIDS-defining conditions arose in five participants, and 26 participants had high-grade abnormal lab results, with nine of these Grade 4 abnormalities, mostly related to renal values.

Discussion Highlights and Implications for Practice

Study limitations included the small sample size and significant number of study discontinuations, which the authors noted may have introduced an element of selection bias.

Study authors believe that these results, along with their prior studies, show injected lenacapavir’s safety and tolerability. Participants who developed resistance to the study drug had suboptimal background regimens, indicating the importance of combining injected lenacapavir with at least one other active antiretroviral.

By Barbara Jungwirth