Long-acting cabotegravir pharmacokinetics with and without oral lead-in for HIV PrEP

• DOI: 10.1128/aac.01475-23
• Publication Date: 2024-05-06T12:49:43Z
• Authors: Kelong Han; Parul Patel; Scott McCallister; Alex R. Rinehart; Yash Gandhi; William Spreen; Raphael J. Landovitz; Sinead Delany-Mor...; Mark A. Marzinke; Todd McKeon; Piotr Budnik; Jean van Wyk; Susan L. Ford
• Keywords: Tolerability

ABSTRACT Long-acting cabotegravir is approved for pre-exposure prophylaxis and combination HIV treatment, both initiated with optional short-term oral lead-in (OLI). We evaluated the impact of OLI on long-acting pharmacokinetics. Cabotegravir plasma concentrations were compared between HIV-positive participants initiating injections ( n = 278) or without 110) in phase III treatment study FLAIR HIV-negative using 263) pivotal studies HPTN 083 084. pharmacokinetic profiles simulated three populations (assigned-male-at-birth, 50%-assigned-female-at-birth, assigned-female-at-birth) under scenarios: first injection given (A) 1 (B) 3 days after final dose (OLI-injection gap) (C) OLI. The PK objective was 80% achieving 4× vitro protein-adjusted 90% maximal inhibitory concentration (PA-IC 90 ) 50% 8× PA-IC . Observed trough C τ similar P > 0.3). With a 3-day OLI-injection gap, pre-injection remained above objective. Approximately 1–2 weeks injection, became nearly identical among all scenarios. Without OLI, it predicted that achieve 1.2, 1.8, 2.8 each population, respectively, 1.4, 2.1, 3.8 days, respectively. exposure supporting use. to remain gaps ≤3 rapidly Findings are consistent assigned-male-at-birth assigned-female-at-birth populations. This registered ClinicalTrials.gov as NCT02720094