An open-label phase IIIb trial known as IMPALA found that a long-acting injectable HIV regimen kept viral suppression comparable to daily oral therapy among people with a history of poor adherence. At 48 weeks, 91% of participants receiving cabotegravir/rilpivirine every eight weeks had a viral load below 50 copies/mL, versus 89.2% of those on a once-daily dolutegravir-based pill. The difference met the prespecified noninferiority threshold.
Researchers enrolled 540 adults at seven sites in Kenya, South Africa, and Uganda; 537 were included in the primary analysis. Adherence challenges were defined as a viral load above 1,000 copies/mL or being more than four weeks late for a visit or refill in the prior two years. Confirmed virologic failure occurred in five people on the injection and none on oral therapy, also meeting noninferiority. The authors say the results support adding long-acting injectables to WHO treatment guidelines.
Adverse events were somewhat more common with the injection: 84.1% reported any event excluding injection-site reactions, versus 76.6% on oral therapy. Injection-site reactions were reported by 37.3%, all grade 1 or 2, and none led to discontinuation. Despite this, 93.6% of those receiving the injection said they preferred it to their previous oral regimen.
The findings build on earlier work, including the CARES and LATITUDE trials, though the researchers caution that LATITUDE's results may not translate to African public health settings due to limited resistance testing and infrequent viral load monitoring. Study limitations include the open-label design and the possibility that clinical trial participation overestimates real-world adherence.