Lenacapavir for HIV Infection in a Multidrug-Resistant Study Cohort

There have been myriad advances in HIV treatment options. Injectable, long-acting HIV therapies, once a pipe dream, are now approved and available.

However, treatments for people living with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) are far more limited. People with difficult-to-treat HIV or a history of treatment failure have substantial treatment needs.

Lenacapavir, a first-in-class capsid inhibitor, has potential to fulfill this need. Today, research from the ongoing phase 3 CAPELLA trial was published in The New England Journal of Medicine. Sorana Segal-Maurer, MD, the principal investigator and lead author of the paper, sat down with Contagion to discuss the significance of these results.

This significance, Segal-Maurer says, largely stems from the study population, who had “pretty resistant virus and not a lot of options for its control.” Of the 72 patients enrolled, 1 in 5 had no fully active antiretrovirals available to them. “These were deeply multidrug-resistant HIV-infected patients,” said Segal-Maurer.

Additionally, the median age of the study population was 52 years, and the average time of HIV infection was 24 years. Treatment failure was common in this cohort, and Segal-Maurer said most had cycled through at least 9 to 11 antiviral agents.

The highly resistant HIV infections in this cohort makes the results all the more remarkable. “Study results can be very rosy if there’s not a lot of disease,” Segal-Maurer said. “But if you have terrific results and you have a really challenging population, I really think that speaks to the importance of the results.”

At week 14 of the study, 81% of participants were undetectable with a viral load of less than 50 copies per milliliter. Segal-Maurer notes that this change was sustained through week 26 of the study.

As a provider herself, Segal-Maurer highlighted the trial results that may be of great interest to other providers: “It’s good to be undetectable, but we want to see a rise in CD4 cells...that really leads to that decrease in opportunistic infections.”

Segal-Maurer emphasized, “EVERYONE who had profoundly decreased CD4 cells were able to get past that point, and I find that incredibly meaningful.”

Findings from the CAPELLA trial were originally presented at the 2021 Annual Conference on Retroviruses and Opportunistic Infections (CROI).

Sorana Segal-Maurer, MD, is Director of Infectious Diseases at New York-Presbyterian Queens and a professor of Clinical Medicine at Weill Cornell Medicine. She is the principal site investigator for the study, "Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection," published in The New England Journal of Medicine.

This is Part 1 of a 2-part interview with lead author and investigator Dr. Sorona Segal-Maurer. Come back tomorrow for Part 2!