Chronic daily oral ART can be lifesaving but also inconvenient, increasing the risks of non-adherence and treatment failure. To address these issues, long-acting (LA) injectable regimens of the INSTI cabotegravir (CAB) and the NNRTI rilpivirine (RPV) are under evaluation. FLAIR (NCT02938520) is a randomized, Phase 3, open-label, multicenter study investigating whether switching to monthly CAB+RPV LA is non-inferior to daily dolutegravir/abacavir/lamivudine (DTG/ABC/3TC [CAR]) in virologically suppressed adults infected with HIV-1.
ART-naive participants received induction therapy with oral CAR for 20 weeks. After 16 weeks, participants with HIV-1 RNA <50c/mL were eligible to enter the maintenance phase (MP) and were randomized (1:1) to either switch to LA or continue CAR. Those randomized to the LA arm received an oral lead-in of CAB 30mg + RPV 25mg once daily for 4 weeks before receiving monthly injectable CAB+RPV LA. The primary endpoint was viral load ≥50c/mL at MP Week 48 (W48) by FDA snapshot algorithm (NI margin 6%). Endpoints assessed at MP Week 96 (W96) included viral loads ≥50c/mL and <50c/mL, confirmed virologic failure (CVF; two consecutive viral loads ≥200c/mL), safety, tolerability, and patient satisfaction.
From 629 participants who initiated induction therapy, 566 were randomized to either the LA or CAR arm (283/arm). Median age was 34y (11% ≥50y); 22% were female and 74% were white. At W96, 9 (3.2%) participants in each arm had HIV-1 RNA ≥50c/mL, underscoring the non-inferiority established at W48 (Table). For the LA arm, the rate of CVF was unchanged from W48 at W96 (4 participants [1.4%]); 3 had mutations in the NNRTI + INSTI domains and 1 had no mutations). The CAR arm had 4 CVFs through W96 (vs. 3 through W48); none had mutations. Across both treatment arms, AEs leading to withdrawal were infrequent. Injection site reactions (ISRs) were the most common drug-related AE (86% of participants in the LA arm); their frequency decreased over time. Median ISR duration was 3 days and 99% were Grade 1 or 2. At W96, the LA regimen was associated with a greater treatment satisfaction vs. oral CAR as measured by HIVTSQs.
CAB+RPV LA maintained viral suppression with no further CVFs between W48 and W96 and was non-inferior to oral standard of care ART. Although ISRs were frequently reported with CAB+RPV LA, they seldom led to withdrawal, and overall treatment satisfaction was higher than with ART. These results attest to the durability of CAB+RPV LA.