Lenacapavir (Sunlenca) every 26 weeks compared with daily antiretroviral therapy (ART) in the phase II CALIBRATE trial was more effective in suppressing HIV than conventional therapy in the first-line setting quite.
All three groups suppressed virus to less than 50 copies/mL by 85-90% at week 54 with oral or subcutaneous administration every 26 weeks (first 28 weeks vs. Combination of two oral ARTs daily) for 1 week, then 1 week later), this was comparable to 94% of daily oral bictegravir, emtricitabine, and tenofovir alafenamide % rates were not significantly different.
“These data suggest that lenacapavir in combination with a second potent drug is effective in maintaining virologic suppression, consistent with previous studies of dual-drug regimens,” Indianapolis Samir K. Gupta, MD, Indiana University School of Medicine, and colleagues in The Lancet HIV.
Lenacapavir is first-in -class inhibitors of capsid activity at multiple points in the viral life cycle. Based on data from the CAPELLA trial, it was recently approved by the FDA for use in heavily pretreated patients with HIV-1 drug-resistant infection, as well as those who cannot tolerate other available options, in combination with ART.
However, lenacavir relies on antiretroviral drugs that need to be taken daily, although studies have found that daily, weekly, or up to every 6-monthly injections are effective.
“These are certainly promising results; however, lenacapavir needs a long-acting partner if it is to deliver on its promise of being part of a complete long-acting therapy,” London, in an accompanying study wrote in the comments. “With unexpected immunological discoveries slowing the development of islatravir, the identity of this partner is far from clear.”
Total lymphopenia and some participation due to drug CD4+ T cell counts of patients.
While no other long-acting antiretroviral drug is currently available, Gupta and coauthors note that “efforts are underway to develop a long-acting partner drug that can be combined with lenacapavir as a full synchronous regimen that offers the best potential for sustained adherence.”
The lenacapavir trial included 182 adult patients randomly assigned to one of four treatment groups. Groups 1 (n=52) and 2 (n=53) were assigned to receive lenacapavir 927 mg subcutaneously every 26 weeks (after 2 weeks of oral loading) in combination with daily oral emtricitabine and tenofovir Lafenamide (Descovy) for 28 weeks. Then after a second subcutaneous dose of ranacavir, group 1 continued to receive 25 mg of tenofovir alafenamide orally per day, while group 2 switched to bictegravir at a dose of 75 mg.
Group 3 of 52 people received daily oral lenacapavir (600 mg on days 1 and 2, then 50 mg per day) plus emtricitabine and tenofovir alafenamide. Group 4 (n=25) served as a control group, and these patients received daily oral administration of bictegravir, emtricitabine, and tenofovir alafenamide.
Of the 182 participants treated, 22 did not complete the study – 17 of whom were in the lenacavir group.
All participants were treatment naïve, had a plasma HIV-1 RNA of at least 200 copies/mL, a CD4 cell count of at least 200 cells/μL, and had no hepatitis B or C Infect. The trial was predominantly male (93%), with the majority of patients either black (52%) or white (43%), 45% of whom were Latino.
The most common adverse events with lenacapavir were injection site reactions, including erythema (27%), swelling (23%), and pain (19%). Other adverse events included headache and nausea (13% each).
Limitations of the study include small sample size, few female participants (12 in total), and limited duration. While several participants discontinued the drug (three due to grade 1 injection site reactions), the researchers said the discontinuation was not due to safety or efficacy.
Ingrid Hein is a staff writer for MedPage Today covering infectious diseases. For more than a decade, she has been a medical journalist. Follow
the Research funded by Gilead Sciences. Gupta reports he has received funding and serves as an advisor at the National Institutes of Health, Gilead, and ViiV Healthcare.
Others reported grants, speaker roles and consulting from Gilead, Merck, ViiV Healthcare, AbbVie and Janssen.
Orkin reported research grants, honoraria and travel fellowships from Gilead, Viiv Healthcare, MSD, Janssen and AstraZeneca.
The Lancet HIV
Source reference: Gupta SK et al “Lenacapavir given every 26 weeks or in combination with daily oral antiretroviral therapy Initial treatment for HIV: A randomized, open-label, active-controlled phase 2 trial” The Lancet HIV 2023; DOI: 10.1016/S2352-3018(22)00291-0.
Source reference: Orkin C “Lenacapavir in first-line therapy” Lancet HIV 2023; DOI: 10.1016/S2352-3018(22)00375-7.