Pharmacokinetics and antiviral activity of cabotegravir and rilpivirine in cerebrospinal fluid following long-acting injectable administration in HIV-infected adults.

Autor:	Letendre SL; University of California San Diego, San Diego, CA, USA., Mills A; Men's Health Foundation, Los Angeles, CA, USA., Hagins D; Chatham County Health Dept, Savannah, GA, USA., Swindells S; University of Nebraska Medical Center, Omaha, NE, USA., Felizarta F; Office of Franco Felizarta, MD, Bakersfield, CA, USA., Devente J; Long Beach Education and Research Consultants, Long Beach, CA, USA., Bettacchi C; North Texas Infectious Diseases Consultants, P.A., Dallas, TX, USA., Lou Y; PAREXEL International, Durham, NC, USA., Ford S; GlaxoSmithKline, Research Triangle Park, NC, USA., Sutton K; ViiV Healthcare, Research Triangle Park, NC, USA., Shaik JS; GlaxoSmithKline, Collegeville, PA, USA., Crauwels H; Janssen Research and Development, Beerse, Belgium., D'Amico R; ViiV Healthcare, Research Triangle Park, NC, USA., Patel P; ViiV Healthcare, Research Triangle Park, NC, USA.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2020 Mar 01; Vol. 75 (3), pp. 648-655.
DOI:	10.1093/jac/dkz504
Abstrakt:	Background: Long-acting (LA) formulations of cabotegravir, an HIV integrase inhibitor, and rilpivirine, an NNRTI, are in development as monthly or 2 monthly intramuscular (IM) injections for maintenance of virological suppression. Objectives: To evaluate cabotegravir and rilpivirine CSF distribution and HIV-1 RNA suppression in plasma and CSF in HIV-infected adults participating in a substudy of the Phase 2b LATTE-2 study (NCT02120352). Methods: Eighteen participants receiving cabotegravir LA 400 mg + rilpivirine LA 600 mg IM [every 4 weeks (Q4W), n = 3] or cabotegravir LA 600 mg + rilpivirine LA 900 mg IM [every 8 weeks (Q8W), n = 15] with plasma HIV-1 RNA <50 copies/mL enrolled. Paired steady-state CSF and plasma concentrations were evaluable in 16 participants obtained 7 (±3) days after an injection visit. HIV-1 RNA in CSF and plasma were assessed contemporaneously using commercial assays. Results: Median total CSF concentrations in Q4W and Q8W groups, respectively, were 0.011 μg/mL and 0.013 μg/mL for cabotegravir (0.30% and 0.34% of the paired plasma concentrations) and 1.84 ng/mL and 1.67 ng/mL for rilpivirine (1.07% and 1.32% of paired plasma concentrations). Cabotegravir and rilpivirine total CSF concentrations exceeded their respective in vitro EC50 for WT HIV-1 (0.10 ng/mL and 0.27 ng/mL, respectively). All 16 participants had HIV-1 RNA <50 copies/mL in plasma and CSF, and 15 of 16 participants had HIV-1 RNA <2 copies/mL in CSF. Conclusions: A dual regimen of cabotegravir LA and rilpivirine LA achieved therapeutic concentrations in the CSF resulting in effective virological control in CSF. (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
Databáze:	MEDLINE
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