March 29, 2023
Lenacapavir for the Initial Treatment of HIVBy Lauren Richey, MD, MPH, FIDSA
Lenacapavir is a new antiretroviral agent with a novel mechanism of action: inhibition of the HIV capsid protein. It also has a novel dosing interval: either orally daily or subcutaneously every 6 months. Lenacapavir was recently FDA approved for use in people with multidrug-resistant HIV, but there is currently no data for its use in the initial treatment of HIV, which is addressed in this study.
The CALIBRATE study was a randomized, open-label study. Treatment-naïve participants were randomly assigned to four different groups, 2:2:2:1, and stratified by HIV viral load (< 100,000 and > 100,000). Group 1 and 2 had an oral loading dose of lenacapavir on days 1, 2, and 8 before beginning subcutaneous lenacapavir on day 15 and repeating injections every 26 weeks. Participants were also given emtricitabine (FTC) and tenofovir alafenamide (TAF) daily through the 28-week induction period. At this point, group 1 participants who were virally suppressed at weeks 16 and 22 switched to a 2-drug regimen of TAF with subcutaneous lenacapavir. In group 2, those who were virally suppressed at weeks 16 and 22 were switched to a 2-drug regimen of bictegravir (BIC) with subcutaneous lenacapavir. Group 3 was given a loading dose of lenacapavir on days 1 and 2 but then maintained on daily oral lenacapavir plus oral FTC and TAF throughout the study. Group 4 received oral 3-drug ART with BIC, FTC, and TAF. The primary efficacy endpoint was the percentage of participants achieving viral suppression at week 54.
Of 182 participants, most were Black (52%) cisgender (93%) males (93%) with a median CD4 count of 437. The primary endpoint of viral suppression was achieved by 90% in group 1, 85% in group 2, 85% in group 3, and 92% in group 4 (the standard of care). Five participants from the lenacapavir groups met the definition of virologic failure, three of whom later re-suppressed without a regimen change and two of whom had lenacapavir resistance-associated mutations attributed to poor adherence to companion drugs. Among participants receiving lenacapavir subcutaneous injections, injection site reactions with erythema, pain, and swelling were common (54%) but not severe. This data supports the use of lenacapavir in initial treatment of HIV with similar viral suppression outcomes to the standard of care.
