Abstract:
Evaluation of the durable efcacy and safety of long-acting injectable
therapy for HIV is needed in African populations. In a multicenter,
open-label phase 3b trial, 512 African adults with HIV-1, stable on frst-line
oral therapy, with screening plasma viral load (VL) <50 copies ml−1 and
without past virologic failure were randomized (1:1) to continue oral therapy
or switch to cabotegravir (600 mg) and rilpivirine (900 mg) intramuscular
injections every 8 weeks (optional 4-week oral lead-in). VL was monitored
every 24 weeks. Here the primary outcome for our analysis up to 96 weeks
was VL <50 copies ml−1, using the Food and Drug Administration snapshot
algorithm (noninferiority margin 10%) in the intention-to-treat exposed
population. At 96 weeks, 247/255 (97%) in the long-acting group and 250/257
(97%) in the oral therapy group had VL <50 copies ml−1 (diference −0.4%; 95%
confdence interval −3.1% to 2.0%), demonstrating noninferiority. Adverse
events of severity grade ≥3 occurred in 41/255 (16%) in the long-acting group
and in 22/257 (9%) in the oral therapy group, mostly considered unrelated to
the study drug; only one treatment-related adverse event in the long-acting
group led to a decision to discontinue treatment (injection-site abscess).
Cabotegravir and rilpivirine long-acting therapy produced durable virologic
suppression, met the prespecifed noninferiority endpoint compared
with oral therapy and demonstrated an acceptable safety and tolerability
profle. Long-acting therapy may be considered for use in African treatment
programs. PACTR registration: 202104874490818.
