Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials

J Infect Dis. 2024 Jul 25;230(1):e34-e42. doi: 10.1093/infdis/jiad580.

Abstract

Background: Cabotegravir plus rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of human immunodeficiency virus-1 (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-2M were pooled through week 48. Data beyond week 48 were summarized by study (FLAIR through week 96 and ATLAS-2M through week 152). HIV-1 RNA <50 and ≥50 copies/mL, confirmed virologic failure (CVF; 2 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 week 48, 92% versus 93% of participants with lower versus higher BMI had HIV-1 RNA <50 copies/mL, respectively. Including data beyond week 48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least 1 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.

Conclusions: CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category.

Clinical trials registration: NCT02938520, NCT02951052, and NCT03299049.

Keywords: BMI; HIV-1; cabotegravir; long-acting; rilpivirine.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / adverse effects
  • Anti-HIV Agents* / pharmacokinetics
  • Anti-HIV Agents* / therapeutic use
  • Body Mass Index*
  • Diketopiperazines
  • Drug Therapy, Combination
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Pyridones* / pharmacokinetics
  • RNA, Viral / blood
  • Rilpivirine* / administration & dosage
  • Rilpivirine* / adverse effects
  • Rilpivirine* / pharmacokinetics
  • Rilpivirine* / therapeutic use
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Rilpivirine
  • Anti-HIV Agents
  • cabotegravir
  • Pyridones
  • RNA, Viral
  • Diketopiperazines

Associated data

  • ClinicalTrials.gov/NCT02938520
  • ClinicalTrials.gov/NCT02951052
  • ClinicalTrials.gov/NCT03299049