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LONG-ACTING CABOTEGRAVIR + RILPIVIRINE AS MAINTENANCE THERAPY: ATLAS WEEK 48 RESULTS
Susan Swindells1, Jaime-Federico Andrade-Villanueva2, Gary J. Richmond3, Giuliano Rizzardini4, Axel Baumgarten5, Maria Del Mar Masia6, Gulam Latiff7, Vadim Pokrovsky8, Joseph M. Mrus9, Jenny O. Huang10, Krischan J. Hudson9, David A. Margolis9, Kimberly Smith9, Peter E. Williams11, William Spreen9
1University of Nebraska Medical Center, Omaha, NE, USA,2University of Guadalajara, Guadalajara, Mexico,3Broward Health Medical Center, Fort Lauderdale, FL, USA,4Fatebenefratelli Sacco Hospital, Milan, Italy,5MIB Infectious Disease Medical Center, Berlin, Germany,6Hospital General Universitario de Elche, Elche, Spain,7Maxwell Centre, Durban, South Africa,8Russia AIDS Federal Center, Moscow, Russian Federation,9ViiV Healthcare, Research Triangle Park, NC, USA,10GlaxoSmithKline, Mississauga, Ontario, Canada,11Janssen, Beerse, Belgium
ATLAS, a phase 3, open-label, multicenter study, was designed to establish whether switching to monthly long-acting (LA) Cabotegravir (CAB) + Rilpivirine (RPV) LA is noninferior to continuing current 3-drug oral ART in adults with virologically suppressed HIV-1 infection.
Eligible participants had HIV-1 RNA <50 c/mL for ≥6 months without virologic failure on oral regimens comprising 2 NRTI + 1 INSTI, NNRTI, or PI. Participants were randomly assigned (1:1) to continue current ART (CART arm) or switch to the LA arm. The LA arm participants received oral CAB 30mg + RPV 25mg once daily for 4 weeks for safety monitoring, then single 3 mL loading doses of CAB LA 600mg (200 mg/mL) and RPV LA 900mg (300 mg/mL) by IM injection, followed by 2 mL IM injections every 4 ± 1 weeks of CAB LA 400mg and RPV LA 600mg. The primary endpoint was HIV-1 RNA ≥50 c/mL at W48, using the FDA snapshot algorithm with a 6% noninferiority margin.
616 participants initiated treatment (308/arm; ITT-E). Median age was 42 yrs (26% ≥50 yrs); 33% were female and 68% white. Baseline regimens included 2 NRTI + 1 NNRTI (50%), INSTI (33%), or PI (17%). At W48, 5 participants (1.6%) in the LA arm and 3 (1.0%) in the CART arm had HIV-1 RNA ≥50 c/mL, meeting noninferiority criteria for the primary endpoint (Table). Similarly, the LA arm was noninferior to CART for the key secondary endpoint of HIV-1 RNA <50 c/mL (93% vs 95%). Three LA and 4 CART participants had confirmed virologic failure (CVF, HIV-1 RNA ≥200 c/mL in consecutive samples). The LA CVFs included 1 with RAM E138A, 1 with E138A+V108I (both having E138A in baseline DNA), and 1 with RT-E138E/K and IN-N155H. The 4 CART CVFs included 1 each of RAMs M184I, M184V+G190S, M230M/I, and 1 with no RAMs. In the LA arm, 231 participants (75%) had injection site pain with 4 participants (1%) withdrawing for these events. Incidences of grade 3/4 and serious AEs were similar across the LA and CART arms; there was 1 death (CART arm). Of the 275 LA arm participants completing HIVTSQc at W48, 98% were more satisfied with CAB LA + RPV LA compared with their daily oral treatment at study entry.
The regimen of monthly injections of CAB LA + RPV LA was noninferior to continued 3-drug oral ART at W48. The LA regimen was generally well tolerated, with low rates of serious AEs and drug- or injection-related withdrawals. Virologic failure was infrequent in both arms. Overall, these results support the therapeutic potential of once-monthly CAB LA + RPV LA.