You are here
CABOTEGRAVIR + RILPIVIRINE EVERY 2 MONTHS IS NONINFERIOR TO MONTHLY: ATLAS-2M STUDY
Edgar T. Overton1, Gary J. Richmond2, Giuliano Rizzardini3, Hans Jaeger4, Catherine Orrell5, Firaya Nagimova6, Fritz Bredeek7, Miguel García-Deltoro8, Paul D. Benn
1University of Alabama at Birmingham, Birmingham, AL, USA,2Broward Health Medical Center, Ft Lauderdale, FL, USA,3Fatebenefratelli Sacco Hospital, Milan, Italy,4MVZ Karlsplatz HIV Research and Clinical Care Center, Munich, Germany,5Desmond Tutu HIV Foundation, Cape Town, South Africa,6Republic Tartarstan AIDS Center, Kazan, Russia,7Metropolis Medical, San Francisco, CA, USA,8Hospital General de Valencia, Valencia, Spain,9ViiV Healthcare, Brentford, UK,10GlaxoSmithKline, Collegeville, PA, USA,11ViiV Healthcare, Research Triangle Park, NC, USA,12Janssen, Beerse, Belgium
The 2-drug regimen of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) dosed i.m. every 4 weeks (Q4W) was noninferior to daily oral 3-drug ART in Phase 3 studies. These results and supportive CAB+RPV LA pharmacokinetics enable regimen evaluation at a longer and potentially more convenient 8-week dosing interval (Q8W).
ATLAS-2M is a multicenter, open-label, Phase 3b noninferiority (NI) study of CAB+RPV LA maintenance therapy administered Q8W (600mg CAB + 900mg RPV) or Q4W (400mg CAB + 600mg RPV) to treatment-experienced, HIV-infected adults. Virologically suppressed individuals on CAB+RPV LA Q4W (ATLAS study rollover) or oral standard-of-care were randomized 1:1 to receive CAB+RPV LA Q8W or Q4W. The primary endpoint at Week 48 was the proportion with plasma HIV-1 RNA ≥50 c/mL (Snapshot, ITT-exposed [ITTe]) with an NI margin of 4%. The key secondary endpoint was the proportion with HIV-1 RNA <50 c/mL (Snapshot, ITTe) with an NI margin of -10%.
1045 participants were randomized and treated with CAB+RPV LA Q8W (n=522) or Q4W (n=523); 27% were female, 73% were white. Median age was 42 years (range 1983); 63% were nave to CAB+RPV LA while 37% transitioned from Q4W CAB+RPV LA in ATLAS. CAB+RPV LA Q8W was noninferior to Q4W dosing in both the primary (1.7% vs 1.0%) and secondary analysis (94.3% vs 93.5%; see Table). There were 8 and 2 confirmed virologic failures (CVFs; 2 sequential measures 200 c/mL) on Q8W and Q4W dosing, respectively; 5 and 0 CVFs, respectively, had archived resistance-associated mutations (RAMs) to RPV (E138A, Y188L, H221Y, Y181C) either alone (n=4) or with a CAB RAM (G140R, n=1) in baseline Peripheral blood mononuclear cells (PBMCs). On-treatment RAMs to RPV (K101E, E138K, M230L), CAB (N155H, Q148R, E138K), or both not present in baseline PBMCs were found in 5/8 Q8W CVFs and both Q4W CVFs. The safety profile was similar for Q4W and Q8W dosing (Table). Injection site reactions (ISRs) were mostly mild or moderate (98% overall) with a median duration of 3 days. Discontinuation for an adverse event occurred in 2% of patients (Q8W, n=12; Q4W, n=13), with 5 (1%) in each group due to ISRs. There was one death (Q8W; sepsis). Of those treated Q8W in ATLAS-2M after 48 weeks of Q4W dosing in ATLAS, 93% (115/124) expressed a preference for Q8W dosing.
Q8W dosing of CAB+RPV LA was noninferior to Q4W dosing and well tolerated. These results support the therapeutic potential of CAB+RPV LA administered every 2 months.