However, unlike wild type virus, the in vitro infectivity of virus variants with decreased SR-BI dependence was inhibited by both human HDL and VLDL. These lipoproteins considerably increased the antiviral potency of the mAbs against both the variants and the wild type virus. In conclusion, HCV variants that are less dependent on SR-BI for host cell entry and spread in vitro can be efficiently blocked

by an anti-SR-BI mAb (designated mAb 16-71) in humanized uPA-SCID mice. This phenomenon might be explained by the presence of human lipoproteins in vivo that enhance the efficacy of the anti-SR-BI specific mAb. These properties, together with the fact that all these variants are more click here susceptible to neutralization by anti-HCV envelope antibodies, reduce their

chance of emerging during anti-SR-BI therapy. Disclosures: Thomas Pietschmann – Advisory Committees or Review Panels: Janssen GmbH, Biotest AG; Speaking and Teaching: MSD Sharp & Dohme GmbH, Essex Pharma GmbH The following people have nothing to disclose: Koen Vercauteren, Naomi Van Den Eede, Ahmed A. Mesalam, Sandrine selleck products Belouzard, Jean Dubuisson, Geert Leroux-Roels, Alfredo Nicosia, Philip Meuleman Aim: To evaluate the effect of multiple doses of 240 mg faldaprevir at steady-state on the pharmacokinetics (PK) of a combined oral contraceptive containing 30 μg ethinylestradiol (EE) and 150 μg levonorgestrel (LNG) in healthy premenopausal female volunteers. Methods: This open-label, 2-period, fixed sequence study started with a run-in period (between Days -56 and -28), where subjects received EE/LNG QD until Day 8. No treatment was provided on Days -7 to -1 to induce withdrawal bleeding. In Period 1, subjects received EE/LNG QD on Days 1 to 13 (Visit

3). Trough PK blood samples were taken on Days 1,11 and 12, with intensive PK blood sampling for EE and LNG on Day 13. Following completion of Period 1, subjects proceeded directly to Period 2 where they received EE/LNG QD and faldaprevir 240 mg QD on Days 14 to 21 (Visit 4; faldaprevir was dosed as 240 mg BID on Day 14 as a loading dose). Trough PK blood samples (faldaprevir, EE and LNG) were taken on Days 14, 19 and 20, with PK profiling blood samples obtained for EE and LNG 4-Aminobutyrate aminotransferase on Day 21. Results: A total of 15/16 subjects completed the study and received all doses of study medication, with 1 subject prematurely discontinuing from study participation due to nausea. Overall, EE and LNG exposures were moderately higher when co-administered with faldaprevir than when administered alone (Table 1). Median t,/2 values were prolonged for both EE (2.4 hours longer) and LNG (4.7 hours longer) when co-administered with faldaprevir. Mean oral clearance and apparent volume of distribution of both EE and LNG were lower (∼30%) when co-administered with faldaprevir.