Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial

作者：M.C. Hosseinipour, Myron S. Cohen, R. Panchia, Y. Zhang, M.A. Marzinke, R. Kofron, A.R. Rinehart, E. Tolley, A. Adeyeye, M. Magnus, D. Margolis, C.W. Hendrix, P. Richardson, S. Li, R.J. Landovitz, J. Sugarman, D. Burns, B. Grinsztejn, L. Cottle, W.R. Spreen, A.Y. Liu, Joe Eron, M. McCauley, S.H. Eshleman, H. Dawood, G. Chau · 发表于：UNC Libraries · 年份：2020 · DOI：10.17615/mnq7-rm09 · 研究领域：Hepatitis C virus research、HIV Research and Treatment、HIV/AIDS drug development and treatment

Background: Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States. Methods and findings: HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy individuals age 18–65 years at low HIV risk were randomized (3:1) to receive CAB or placebo (PBO). In the initial oral phase, participants received 1 daily oral tablet (CAB or PBO) for 4 weeks. Those without safety concerns in the oral phase continued and received injections in the injection phase (Cohort 1: 3 injections of CAB LA 800 mg or 0.9% saline as PBO IM every 12 weeks for 3 injection cycles; Cohort 2: CAB LA 600 mg or PBO IM for 5 injection cycles; the first 2 injections in Cohort 2 were separated by 4 weeks, the rest by 8 weeks). The primary analysis included weeks 5 to 41 of study participation, encompassing the injection phase. The cohorts were enrolled sequentially. Primary outcomes were safety and tolerability. Secondary outcomes included pharmacokinetics and events ...