title: Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers.
abstract: 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.
  
  
  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.
authors.affiliation: aFundació LLuita contra la Sida Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona bUnidad de Endoscopia Digestiva, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Catalonia, Spain cFundació IrsiCaixa, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Catalonia, Spain dPharmacology Research Laboratories, Liverpool, UK eUniversitat de VIC- Universitat Central de Catalunya (VIC-UCC) fBCN Checkpoint, Barcelona, Spain gDepartment of Molecular and Clinical Pharmacology, University of Liverpool, UK.
authors.forename: Josep
authors.initials: J
authors.lastname: Coll
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Jaume
authors.initials: J
authors.lastname: Boix
authors.forename: Elisabet
authors.initials: E
authors.lastname: Gómez-Mora
authors.forename: Laura
authors.initials: L
authors.lastname: Else
authors.forename: Elisabet
authors.initials: E
authors.lastname: García
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Dan
authors.initials: D
authors.lastname: Ouchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrillo
authors.forename: Roser
authors.initials: R
authors.lastname: Escrig
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cabrera
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D001706:Biopsy; D003510:Cyclohexanes / Q000008:administration & dosage*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000302:isolation & purification*; D064368:Healthy Volunteers; D006801:Humans; D007413:Intestinal Mucosa / Q000821:virology*; D000077592:Maraviroc; D008954:Models, Biological; D009940:Organoids / Q000821:virology*; D017211:Treatment Failure; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc