Background
IMPAACT 2017 (MOCHA) evaluated the safety, tolerability, and pharmacokinetics (PK) of the first all-injectable long-acting (LA) antiretroviral therapy (ART) of intramuscular (IM) cabotegravir (CAB) + rilpivirine (RPV) in virologically suppressed (HIV-1 RNA <50 c/mL) adolescents with HIV. Data through Week 96 and end-of-study are presented.
Methods
In this Phase I/II noncomparative trial, virologically suppressed adolescents (12 to <18 years;≥35 kg) switched from pre-study ART to 4 weeks of daily oral CAB+RPV followed by 600mg CAB-LA + 900mg RPV-LA IM (3-mL each) at Weeks 4 and 8, and then every 8-weeks for 96 weeks with an optional extension phase for up to an additional 48 weeks.
Results
18 centers in 5 countries enrolled 144 participants: median (range) age 15 years (12,17), body mass index 19.5 kg/m2(16.0,34.3), weight 48.5 kg (35.2,100.9), 51% female, 74% Black, and 92% vertically acquired infection. Most (137/144; 95%) participants completed Week 96 with median exposure 137.5 weeks (2, 156); majority (137/144; 95%) receiving ≥ 13 injections. Sixty of 144 (42%) participants experienced a drug-related adverse event (AE), including two Grade 3 AEs (pain and abscess[n=1]; abscess[n=1]; both resolved) and one Grade 4 AE (anaphylaxis per site; post-injection reaction per protocol team; resolved but led to study drug discontinuation). Of 142 participants with at least one injection, 52 (37%) reported 346 injection site (IS) reactions, majority IS pain (312 instances) assessed as Grade 1 (92%) and lasting ≤7 days (88%). More participants reported “Hurts little more” or higher amount of pain, per the Faces Pain Scale-Revised, with RPV-LA (31%) vs. CAB-LA (16%) at Week 96. All (135/135) preferred LA injections to daily oral ART at Week 96 (injection 13). No confirmed virologic failures (i.e., 2 consecutive viral loads ≥200 c/mL from 2 specimens) occurred through Week 96. Median (5th-95th%) Week 96 observed CAB (2.96 µg/mL [1.40-5.52]) and RPV (89.5 ng/mL [54.1-152.0]) troughs approximated those in adults, exceeded the protein-adjusted IC90 of 0.166 μg/mL and 12 ng/mL for CAB and RPV, respectively and appeared at steady state for CAB but not RPV (Figure).
Conclusions
Week 96 and End-of-study data from the first study in virologically suppressed adolescents who switched from daily oral ART to IM CAB-LA + RPV-LA every 8-weeks demonstrate an acceptable safety/PK profile, sustained viral suppression, strong participant preference and inform the global use of this all-injectable treatment regimen.
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