Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers

Josep Coll, José Moltó, Jaume Boix, Elisabet Gómez-Mora, Laura Else, Elisabet García, Roger Paredes, Dan Ouchi, Antonio Carrillo, Roser Escrig, David Back, Bonaventura Clotet, Cecilia Cabrera

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

© Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved. Objective: Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans. Design and Methods: Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600 mg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200 mg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4 h after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation. Results: Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1 ng/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells. Conclusions: An ex-vivo challenge with a single oral dose of MVC does not prevent ex-vivo infection of human rectal mucosa. The lack of prophylactic efficacy observed suggests that 'on demand' MVC preexposure prophylaxis would not prevent rectal HIV-1 transmission.
Original languageEnglish
Pages (from-to)2149-2154
JournalAIDS
Volume29
Issue number16
DOIs
Publication statusPublished - 23 Oct 2015

Keywords

  • 'on demand' preexposure prophylaxis
  • ex-vivo challenge
  • ex-vivo tissue culture
  • maraviroc
  • single oral dose

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