Through 52 weeks of treatment, a regimen containing injectable lenacapavir appears promising in treatment-experienced people living with multidrug-resistant HIV, a recently published study found. However, the sample size was small and mostly male, potentially limiting the applicability of the findings.
About This Study
“Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial” was published online on July 11, 2023, in The Lancet HIV. The lead author is Onyema Ogbuagu, M.D., of the Yale University School of Medicine in New Haven, Connecticut. Some study authors are from Gilead Sciences, the manufacturer of the study drug. A related commentary, “Lenacapavir: an attractive option, but proceed with caution,” was written by by Marianne Harris, M.D., of the British Columbia Centre for Excellence in HIV/AIDS and the Department of Family Practice in the Faculty of Medicine at the University of British Columbia, Vancouver, Canada.
Key Research Findings
The CAPELLA study investigates combining an optimized background regimen with subcutaneous injections of the capsid inhibitor lenacapavir in people with severe HIV disease and multidrug-resistant virus. After a two-week oral lead-in period, the study drug is injected subcutaneously every six months.
At baseline, the 72 participants had a median CD4 cell count of 150 cells/µL and the virus in 46% of participants was resistant to all four major drug classes. Seventy-five percent of participants were male at birth, the median age was 52 years, while 41% of participants were white, 38% Black, and 21% Asian.
By week 52, 78% of participants were virally suppressed. Resistance to the study drug emerged in nine people, mostly due to lack of effective drugs for the background regimen and/or adherence challenges. Sixty-five percent of participants experienced study drug-related injection site reactions.
Discussion Highlights and Implications for Practice
Study limitations included the small sample size, and oral administration of the drug in some participants while the injectable version was put on hold by the U.S. Food and Drug Administration.
While results seem promising, longer-term hypersensitivity reactions are possible, cautioned Marianne Harris in the accompanying commentary. So far, the study drug has only been tested in 229 people, 30 of whom were assigned female at birth. The drug remains in the body for more than nine months after injection, making treatment of adverse reactions challenging.
Study authors suggested that their results support starting oral lead-in and injections of the study drug on the same day, while Harris countered that this conclusion is premature and larger, more diverse trials are needed before taking that step.