Long-acting ART safe, effective at 124 weeks
Long-acting injectable cabotegravir plus rilpivirine effectively maintained viral suppression of HIV among adults with or without a 1-month oral lead-in phase, according to the results of a study published in The Lancet HIV.
The FDA approved the once-monthly injectable regimen, branded as Cabenuva, in January.
“This is the longest follow-up data on people who have received long-acting injectable cabotegravir plus rilpivirine as part of a phase 3 clinical trial,” Chloe Orkin, MBBCh, professor, consultant physician and HIV research lead at Queen Mary University of London and Barts Health, told Healio. “It provides reassurance on durability.”
The new results are from the FLAIR study an ongoing phase 3, randomized, open-label, multicenter trial that previously reported improved treatment satisfaction compared with daily ART at 96 weeks.
Orkin and colleagues assessed 124-week safety, tolerability and durability of the regimen among ART-naive participants who were virologically suppressed during the 20-week induction phase with standard of care. They randomly assigned the participants in a 1:1 ratio to continue the standard of care oral regimen or switch to the long-acting regimen in the 100-week maintenance phase.
According to the study, randomization was stratified by sex at birth and baseline HIV-1 RNA. Participants in the treatment group received cabotegravir plus rilpivirine once daily for at least 4 weeks before their first injection. They could choose to continue long-acting cabotegravir (400 mg) plus rilpivirine (600 mg) every 4 weeks from week 100 or withdraw.
Study endpoints for week 124 included plasma HIV-1 RNA of at least 50 copies/mL or less than 50 copies/mL, confirmed virological failure — HIV-1 RNA measured at 200 copies/mL or higher two times in a row — safety and tolerability.
According to the study, at week 100, 232 (92%) of 253 participants transitioned to long-acting cabotegravir plus rilpivirine in the extension phase (111 in the direct-to-injection group and 121 in the oral lead-in group), whereas 243 of the 283 who were randomly assigned to the long-acting therapy group continued the long-acting regimen into the extension phase.
Orkin and colleagues found that less than 1% of participants in each extension switch group HIV-1 RNA of 50 or more copies/mL, whereas 99% of participants in the direct-to-injection group and 93% in the oral lead-in group remained suppressed at the week 124 check-in.
The researchers said the lower suppression rates in the oral lead-in group were driven by nonvirological reasons. Additionally, the study showed that among participants who were randomly assigned to the long-acting therapy group, 80% remained suppressed.
Adverse events leading to withdrawal occurred in three participants in the extension switch population and two in the oral lead-in group after 24 weeks of therapy, and in 15 people in the randomly assigned long-acting group, with injection site reactions being the most common.
“Long-acting injectable cabotegravir and rilpivrine was effective and safe over 124 weeks of treatment,” Orkin concluded. “The outcomes were good in those people who chose not to have the oral lead-in.”