Cabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly monthly or every 2 months is a complete long-acting (LA) regimen for the maintenance of HIV-1 virologic suppression. The ATLAS-2M (NCT03299049) Week (W) 48 primary and W96 secondary analyses demonstrated noninferiority of CAB+RPV LA administered every 8 weeks (Q8W) vs. every 4 weeks (Q4W). Here, we report the W152 results.
ATLAS-2M is a Phase 3b, randomized, multicenter study assessing the efficacy and safety of CAB+RPV LA Q8W vs. Q4W. Virologically suppressed (HIV-1 RNA <50 copies/mL) individuals receiving CAB+RPV LA Q4W (ATLAS [NCT02951052] study rollover) or oral therapy were randomized 1:1 to receive CAB+RPV LA Q8W or Q4W. The primary endpoint was the proportion of participants with plasma HIV-1 RNA ?50 copies/mL (FDA Snapshot; 4% noninferiority margin). Other endpoints included proportion of participants with plasma HIV-1 RNA <50 copies/mL, incidence of confirmed virologic failure (CVF; two consecutive plasma HIV-1 RNA ?200 copies/mL), tolerability, and safety.
1045 participants received CAB+RPV LA (Q8W, n=522; Q4W, n=523). Median (range) age was 42 years (19–83); 27% were female (sex at birth) and 73% were White. At W152, CAB+RPV LA Q8W demonstrated noninferior efficacy vs. Q4W dosing, with 2.7% (n=14) and 1.0% (n=5) of participants having HIV-1 RNA ?50 copies/mL in each arm, and the confidence interval excluded the noninferiority margin (Table). High levels of virologic suppression were observed; 86–87% of participants maintained HIV-1 RNA <50 copies/mL. Further, 11 (2.1%) and 2 (0.4%) participants in the Q8W and Q4W arms had CVF, representing an additional 2 since the W96 analysis. Both were in the Q8W arm and had treatment-emergent resistance-associated mutations to RPV (E138A+Y181Y/C; E138A+M230M/L) and CAB (Q148R). Safety profiles were comparable, with no new significant safety information observed. Injection site reactions were the most common adverse event; most were mild or moderate in severity (98.9%), with a median duration of 3 days, and few participants discontinued due to injection-related reasons.
Efficacy of CAB+RPV LA Q8W continued to be noninferior to Q4W at W152, with both regimens maintaining high levels of virologic suppression. The overall incidence of CVF was low, with two additional cases reported in the Q8W arm after W96. These data further support CAB+RPV LA as a complete regimen for the maintenance of HIV-1 virologic suppression.