TY - JOUR
T1 - Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers
AU - Coll, Josep
AU - Moltó, José
AU - Boix, Jaume
AU - Gómez-Mora, Elisabet
AU - Else, Laura
AU - García, Elisabet
AU - Paredes, Roger
AU - Ouchi, Dan
AU - Carrillo, Antonio
AU - Escrig, Roser
AU - Back, David
AU - Clotet, Bonaventura
AU - Cabrera, Cecilia
PY - 2015/10/23
Y1 - 2015/10/23
N2 - © 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.
AB - © 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.
KW - 'on demand' preexposure prophylaxis
KW - ex-vivo challenge
KW - ex-vivo tissue culture
KW - maraviroc
KW - single oral dose
U2 - 10.1097/QAD.0000000000000769
DO - 10.1097/QAD.0000000000000769
M3 - Article
VL - 29
SP - 2149
EP - 2154
IS - 16
ER -
