Long-acting cabotegravir (CAB-LA) plus long-acting rilpivirine (RPV-LA) are now approved for maintenance of viral suppression in adults with HIV-1 infection. IMPAACT 2017 (MOCHA) is a phase I/II non-comparative, open label study to confirm the dose and evaluate safety, tolerability, acceptability, and pharmacokinetics (PK) of oral CAB, CAB-LA, and RPV-LA in adolescents, ?12 to <18 years, living with HIV-1. Here we present data-to-date from Cohort 1, Q4W, of the study.
Virologically suppressed (viral load <50 copies/mL) adolescents living with HIV-1 and on stable combination antiretroviral therapy (cART) were enrolled into Cohort 1C (CAB) or Cohort 1R (RPV) based on background cART. After 4 weeks of oral lead-in with either CAB (30mg once daily) or RPV (25mg once daily), participants received CAB-LA (600mg/3mL at Week 4 and 400mg/2mL at Weeks 8 and 12) or RPV-LA (900mg/3mL at Week 4 and 600mg/2mL at Weeks 8 and 12) by gluteal intramuscular (IM) injection. Background cART was retained throughout Cohort 1. PK samples were drawn at Week 2 (to assess oral dosing) and Weeks 4, 5, 6, 8, 12, 13, 14 and 16 (to assess LA dosing).
At the time of this analysis, 23 participants enrolled with two premature treatment discontinuations of study drug, both in Cohort 1R; one due to hypersensitivity (after 1st oral dose) and one due to pain with needle insertion prior to receiving first IM injection. Cohort 1C included 6 males and 2 females with median (range) age 14.5 (12-17) years and weight 57 (43-73.5) kg; Cohort 1R included 7 males and 8 females with median (range) age 17.0 (12-17) years and weight 63 (44.1-98.5) kg. All injection site reactions were grade 1 or 2 and none led to discontinuation. Through Week 16 there was one Grade 3 drug-related adverse event in each cohort (insomnia, 1C) and (hypersensitivity, 1R, leading to study withdrawal). The median PK parameters were within the desired study targets, based on achieving comparable exposure in adolescents and adults with median (range) presented. Cohort 1C Week 2 Oral CAB AUC0-?: 160 (94.3-325) mcg*h/mL (target median 46-277), Week 16 IM CAB trough: 3.11 (1.22-6.19) mcg/mL (target median 0.71-6.7). Cohort 1R Week 16 IM RPV trough: 52.9 (31.9-148) ng/mL (target for median 25-100).
IM administration of CAB-LA or RPV-LA in adolescents achieved target exposure concentrations consistent with predictions and were comparable to adults receiving monthly IM dose regimens. No new or unanticipated safety concerns were identified.