Abstract Body

Background:

Cabotegravir (CAB) + rilpivirine (RPV) long-acting (LA) administered via gluteal intramuscular (IM) injections is recommended by treatment guidelines for maintaining HIV-1 virologic suppression. Previous data in healthy participants receiving single CAB+RPV LA IM injections to the vastus lateralis (thigh muscle) were supportive of further evaluation. Here we present the results of a substudy evaluating the pharmacokinetics (PK), safety, tolerability, and efficacy of CAB+RPV LA following short-term repeat IM thigh administration in adults with HIV-1 who had received ≥3 years of gluteal injections while participating in the ongoing Phase 3b ATLAS‑2M study.

Methods:

ATLAS-2M participants volunteered and reconsented for the substudy, which included a screening phase, thigh injection phase [Day 1–Week (W) 16], and return to gluteal injection phase (W16–24). The substudy injection schedule was unchanged from the main study [every 8 week arm (Q8W) arm, CAB 600 mg + RPV 900 mg; every 4 week (Q4W) arm, CAB 400 mg + RPV 600 mg]. CAB and RPV PK parameters following the last thigh gluteal injections and first and last thigh injections were determined by noncompartmental analysis and compared by mixed-effects modeling. Safety, tolerability, participant-reported outcomes, and efficacy were assessed.

Results:

118 participants (Q8W, n=54; Q4W, n=64) enrolled; median (range) age was 48 years (24–71), 38% were female sex at birth, 82% were White. In the Q8W arm, first CAB thigh injection AUC(0–t) and Cmax, first RPV thigh injection Cmax, and all last RPV thigh injection parameters were statistically higher vs. gluteal injections. No statistically significant differences occurred in the Q4W arm (Table). No participants had HIV-1 RNA ≥50 c/mL during the substudy; 3 per arm withdrew for non-virologic reasons. Across 210 Q8W and 494 Q4W thigh injections, 132 and 195 injection site reactions (ISRs) occurred, respectively; most were Grade 1 (55–76%) or 2 (19–38%), with 4–7% Grade 3. The median duration of ISRs was 3–3.5 days. One Grade 2 ISR led to withdrawal. Overall, 28–33% preferred thigh injections, largely due to ease of access.

Conclusions:

CAB and RPV parameters following 16 weeks of thigh injections were similar to gluteal administration, with no clinically significant differences observed. These results support rotational/short-term CAB+RPV LA IM lateral thigh administration within an established gluteal regimen. Additional analyses will assess the potential for early or chronic thigh administration.

Table. Geometric Least Squares Mean Ratios and 90% Confidence Intervals for CAB and RPV Parameters Following Thigh (Test) and Gluteal (Reference) Administration by Injection Interval and Treatment Arm (Paired Data)