Efficacy, safety, and pharmacokinetics by BMI category in Phase 3/3b cabotegravir + rilpivirine long-acting trials.

BACKGROUND:Cabotegravir + rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of HIV-1 virologic suppression. This post hoc analysis summarizes CAB + RPV LA results by baseline body mass index (BMI) category among Phase 3/3b trial participants. METHODS:Data from CAB + RPV-naive participants receiving every 4 or 8 week dosing in FLAIR, ATLAS, and ATLAS-2 M were pooled through Week (W) 48. Data beyond W48 were summarized by study (FLAIR through W96 and ATLAS-2 M through W152). HIV 1 RNA <50 and ≥50 copies/mL, confirmed virologic failure (CVF; two consecutive HIV-1 RNA ≥200 copies/mL), safety and tolerability, and plasma CAB and RPV trough concentrations were evaluated by baseline BMI (<30 kg/m2 [lower];  ≥ 30 kg/m2 [higher]). RESULTS:Among 1245 CAB + RPV LA participants, 213 (17%) had a baseline BMI ≥30 kg/m2. At W48, 92% vs. 93% of participants with lower vs. higher BMI had HIV-1 RNA <50 copies/mL, respectively. Including data beyond W48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least one other baseline factor associated with CVF (archived RPV resistance-associated mutations or HIV 1 subtype A6/A1). Safety and pharmacokinetic profiles were comparable between BMI categories. CONCLUSION:CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category.Main point summary: CAB + RPV LA is effective in the maintenance of HIV-1 virologic suppression in adults regardless of BMI category, with longer-length needles (≥2 inches) recommend for those with BMI ≥30 kg/m2 to accommodate individual body habitus and ensure appropriate administration.