by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
April 21, 2020
Orkin C et al. LONG-ACTING CABOTEGRAVIR + RILPIVIRINE FOR HIV TREATMENT: FLAIR WEEK 96 RESULTS. CROI 2020 | Boston, MA. # 482
The 48-week data on the FLAIR study investigating the use of two long-acting (LA) injectable agents – the INSTI cabotegravir (CAB) and the NNRTI rilpivirine (RPV) were recently published in the NEJM and discussed here (March 24, 2020). At CROI, the 96-week data from the study were presented. The trial included 566 ART-naïve patients who were virologically suppressed (HIV-1 RNA < 50 c/mL) while taking a three-drug oral regimen of dolutegravir/abacavir/lamivudine. After 16 weeks, participants were randomized (1:1) to either continued oral therapy or switch to CAB + RPV given as two IM injections every four weeks. Those randomized to the CAB/RPV arm first received oral formulations of these agent for four weeks. The two endpoints assessed at 96 weeks were subjects with viral loads ≥50c/mL and <50c/mL. Confirmed virologic failures included those with two consecutive viral loads ≥200c/mL. At week 96, only 9 (3.2%) participants in each arm had viral loads > 50c/mL, confirming non-inferiority seen at week 48. The rate of virologic failure in the CAB + RPV was unchanged at about 1% from week 48 to week 96. Of these 4 participants, three had NNRTI mutations and one had an INSTI mutation. The rate of failure was the same (n=4) in the oral therapy arms. Across both arms, adverse events were uncommon and led to treatment withdrawal in only 1% in the oral therapy arm and 4% in the IM arm. Injection site reactions were the most common drug-related AE but their frequency decreased over time. Moreover, at week 96 those receiving the IM therapy reported greater overall treatment satisfaction compared to those in the oral therapy arm. These results attest to the durability of CAB+RPV LA. An extension phase of the FLAIR study is ongoing.
These data complement the 96-week data from ATLAS 2M and provide additional evidence for the efficacy and tolerability of long-acting injectable ART. On March 20th, IM cabotegravir plus rilpivirine (Cabenuva®) was approved for use in Canada. As noted in my commentary on ATLAS2M, I would anticipate having these agents available sometime during 2020 with hopefully an 8-week treatment option for patients. The initial FDA approval of Cabotegravir-Rilpivirine was expected in December 2019 but reportedly delayed due to manufacturing problems and not specifically efficacy or safety concerns.