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LONG-ACTING CABOTEGRAVIR + RILPIVIRINE FOR HIV MAINTENANCE: FLAIR WEEK 48 RESULTS
Chloe Orkin1, Keikawus Arastéh2, Miguel Górgolas Hernández-Mora3, Vadim Pokrovsky4, Edgar T. Overton5, Pierre-Marie Girard6, Shinichi Oka7, Ronald D’Amico8, David Dorey9, Sandy Griffith8, David A. Margolis8, Peter E. Williams10, Wim Parys10, William Spreen8
1Queen Mary University of London, London, UK,2EPIMED GmbH, Berlin, Germany,3Fundacion Jimenez Diaz, Madrid, Spain,4Central Research Institute of Epidemiology, Moscow, Russian Federation,5University of Alabama at Birmingham, Birmingham, AL, USA,6Hôpital Saint Antoine, Paris, France,7National Center for Global Health and Medicine, Tokyo, Japan,8ViiV Healthcare, Research Triangle Park, NC, USA,9GlaxoSmithKline, Mississauga, Canada,10Janssen Research & Development, Beerse, Belgium
The 2-drug long-acting (LA) injectable regimen of the INSTI cabotegravir (CAB) and the NNRTI rilpivirine (RPV) is being developed to reduce dose frequency, pill taking and drug exposure. FLAIR, a phase 3, open-label, multicenter study is investigating whether switching to monthly CAB+RPV is noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC).
ART-naïve participants received induction therapy with oral DTG/ABC/3TC (CAR[sup]&[/sup]) for 20 weeks. Those with HIV-1 RNA <50 c/mL at 16 weeks were eligible to enter the maintenance phase and randomly assigned (1:1) to continue CAR or switch to LA. Participants in the LA arm received an oral lead-in of CAB 30mg + RPV 25mg once daily for 4 weeks to assess tolerability before receiving CAB+RPV as intramuscular monthly LA injectable therapy. The primary endpoint was viral load (VL) ≥50 c/mL at W48 by FDA snapshot algorithm (NI margin 6%). Safety, tolerability and confirmed virologic failure (CVF) were secondary endpoints.
566/629 participants who initiated induction therapy were randomly assigned to the LA or CAR arm (283/arm). The median age was 34 yr (11% ≥50 yr); 22% were female and 74% were white. At the induction phase start, median CD4 count was 444 cells/mm³ (7% <200 cells/mm³), median VL was 4.49 log10 c/mL (20% ≥100,000 c/mL). Six participants in the LA arm (2.1%) and 7 in the CAR arm (2.5%) had HIV-1 RNA ≥50 c/mL at W48, meeting noninferiority criteria for the primary endpoint (Table) and for the key secondary endpoint of HIV-1 RNA <50 c/mL (LA 93.6% vs CAR 93.3%). Four LA recipients (1.4%) had CVF; 3 had mutations in the NNRTI + INSTI domains (K101K/E/Q + G140R, E138K + Q148R, and E138E/A/K/T + Q148R, respectively) and 1 was not tested (PO only). The CAR arm had 3 CVFs with no INSTI resistance. Adverse events (AE) leading to withdrawal and serious AE were infrequent in both arms. The most common drug-related AE was injection site reactions (ISRs; 82% of participants in the LA arm); frequency decreased over time. 99% of ISRs were Grade 1 or 2; the median duration was 3 days. Of 263 LA participants completing HIVTSQc at W48, 99% were more satisfied with CAB+RPV compared with their prior daily oral CAR.
The regimen of monthly injections of CAB+RPV was noninferior to DTG/ABC/3TC at W48. The LA regimen was generally well tolerated with few CVFs. Overall, these results demonstrated the therapeutic potential of CAB+RPV injections, following short initial induction with oral DTG/ABC/3TC to achieve viral suppression.