Lenacapavir (Sunlenca), administered every 26 weeks alongside daily antiretroviral therapy (ART), showed comparable HIV suppression. At week 54, viral suppression to fewer than 50 copies/mL was achieved in 85-90% of participants across three groups receiving lenacapavir, whether orally or subcutaneously every 26 weeks, combined with two daily oral ART drugs for the first 28 weeks, and one afterward. This was not significantly different from the 94% suppression rate with the daily oral regimen of Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide).
“These findings indicate that lenacapavir combined with a second potent agent can effectively maintain viral suppression, consistent with previous two-drug regimen studies,” reported Dr. Samir K. Gupta of Indiana University School of Medicine and colleagues in The Lancet HIV.
Lenacapavir, a first-in-class capsid inhibitor active at multiple stages of the HIV lifecycle, recently received FDA approval for patients with drug-resistant HIV-1 or those unable to tolerate other treatments, based on data from the CAPELLA trial. Despite its success when used daily, weekly, or as an injectable every 6 months, lenacapavir relies on daily antiretroviral drugs.
“These results are undoubtedly promising; however, lenacapavir needs a long-acting partner to realize its potential as part of a complete long-acting regimen,” remarked Dr. Chloe Orkin of Queen Mary University in London, in an accompanying commentary. She noted that the development of islatravir, a potential partner drug, has stalled due to unexpected immunological effects.
Islatravir trials were paused after some participants experienced reductions in total lymphocyte and CD4+ T-cell counts. While no long-acting antiretroviral partners are currently available, Gupta and colleagues emphasized the ongoing search for such an agent to combine with lenacapavir for a more reliable, long-term treatment option.
The trial included 182 participants, randomized into four groups. Group 1 (n=52) and group 2 (n=53) received 927 mg of subcutaneous lenacapavir every 26 weeks (following two weeks of oral loading), combined with daily oral emtricitabine and tenofovir alafenamide (Descovy) for 28 weeks. After the second dose of lenacapavir, group 1 continued on tenofovir alafenamide, while group 2 switched to 75 mg of bictegravir. Group 3 (n=52) received daily oral lenacapavir (600 mg on days 1 and 2, then 50 mg daily) plus emtricitabine and tenofovir alafenamide. Group 4 (n=25), the control group, was given the standard daily oral regimen of bictegravir, emtricitabine, and tenofovir alafenamide.
Of the 182 participants, 22 did not complete the study, with 17 dropouts from the lenacapavir groups. All participants were treatment-naive with plasma HIV-1 RNA levels of at least 200 copies/mL and CD4 counts of 200 cells/μL or more. Most participants were male (93%), with 52% Black, 43% white, and 45% identifying as Latinx.
Common adverse events in the lenacapavir groups included injection-site reactions such as erythema (27%), swelling (23%), and pain (19%). Headaches and nausea occurred in 13% of participants. Study limitations included a small sample size, limited female representation (only 12 women), and short duration. Despite some discontinuations, including three due to grade 1 injection-site reactions, the researchers found no significant safety or efficacy concerns.
