Brief Report: Pharmacokinetic/Pharmacodynamic Investigation of Single-Dose Oral Maraviroc in the Context of HIV-1 Pre-exposure Prophylaxis

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Fox, J, Tiraboschi, JM, Herrera, C, Else, L, Egan, D, Dickinson, L ORCID: 0000-0001-5557-9396, Jackson, A ORCID: 0000-0002-4574-544X, Olejniczak, N, Back, D, Khoo, S ORCID: 0000-0002-2769-0967 et al (show 2 more authors) , Shattock, R and Boffito, M (2016) Brief Report: Pharmacokinetic/Pharmacodynamic Investigation of Single-Dose Oral Maraviroc in the Context of HIV-1 Pre-exposure Prophylaxis Journal of Acquired Immune Deficiency Syndromes, 73 (3). pp. 252-257. ISSN 1525-4135, 1077-9450

Text MVC PREP manuscript final verison 17052016_FINAL.docx - Author Accepted Manuscript Download (2MB)

Abstract

To investigate the pharmacokinetics/pharmacodynamics of single-dose maraviroc 300 mg in HIV-1 exposure compartments. Maraviroc concentrations in blood, secretions (vaginal, urethral, oral, and rectal), and tissue (vaginal and rectal) were measured, and ex vivo challenge was performed in 54 healthy volunteers to study protection from HIV infection. Maraviroc Cmax occurred within 4 hours in most compartments. Concentrations from 4 to 72 hours were above intracellular (IC) IC 90 in all compartments, range 15-8095 ng/mL. Mean AUC 0-72 compartment-to-plasma ratios were highest in the rectum (45-819) and urethra (144) compared with the female genital tract (1.6-4.8) and saliva (0.2). No sex differences in AUC0-72 or Cmax were observed. No ex vivo protection from HIV-1BaL occurred in rectal or vaginal tissue. Despite high and sustained concentrations, single-dose maraviroc was not protective against ex vivo challenge of vaginal/rectal tissue.

Item Type:	Article
Uncontrolled Keywords:	Intestinal Mucosa, Rectum, Vagina, Urethra, Saliva, Humans, HIV-1, HIV Infections, Cyclohexanes, Triazoles, HIV Fusion Inhibitors, Treatment Outcome, Administration, Oral, Models, Biological, Adult, Female, Male, Randomized Controlled Trials as Topic, Healthy Volunteers, CCR5 Receptor Antagonists, Pre-Exposure Prophylaxis, Maraviroc
Depositing User:	Symplectic Admin
Date Deposited:	31 Oct 2016 15:23
Last Modified:	24 Jan 2026 00:55
DOI:	10.1097/QAI.0000000000001108
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3004226
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