A was dosed 100 mg BID and D 60 mg QD. Blood samples for drug assays were drawn during a dosing interval at day 0 (D0) before and 8 weeks (W8) after PR initiation (W8 = 4 weeks after AD initiation). Drugs were assayed by validated LC/MS/MS. Pharmacokinetic (PK) parameters, maximal concentration (Cmax), time to Cmax (Tmax) and predose concentration (Cmin) were Z-VAD-FMK molecular weight observed data; AUC during a dosing interval were estimated by non compartmental method (Win-NonLin®). Results are shown as median and (range).
Geometric mean ratio (GMR) W8/D0 and 90%CI were estimated for RAL parameters. Eighteen of 20 pts were male, median age was 49 (37-59), weight was 74 (65 – 78) kg, CD4 count was 849 (362 – 1994) /mm3, plasma HCV-RNA was 6.11 (4.987.41) log10 UI/mL, and HCV
genotype was 1a in 11 pts and 4 in 9 pts. In addition, 65% were IV drug users, all but 1 pt had plasma HIV-RNA<50 copies/mL, and 7 (35%) had Child A liver cirrhosis. Cmax, Cmin and AUC of A and D at W8 for the 20 pts were 305 (106-1100) ng/mL, 30 (12-144) ng/mL and 1025 (602-3436) ng.h/mL and 1140 (444-2880) ng/mL, 192 (104-641) ng/mL and 12008 (6026-32500) ng.h/mL respectively. For the 7 patients with liver cirrhosis, PK parameters are presented on the table. RAL PK data in the remaining non cirrhotic pts will be presented. All 20 patients had plasma HIV-RNA selleck kinase inhibitor <50 copies/mL at W8. One neutropenia was reported as severe adverse event during the PK study. In conclusion, AD exposure in HIV-HCV co-infected patients was in the same range as in mono-infected patients, and RAL PK remained within a similar range after ADPR initiation in cirrhotic patients despite large inter- and intrapatient PK variabilities as previously reported. Disclosures: Eric Rosenthal - Board Membership: gilead, msd Hugues Aumattre - Speaking and Teaching: BMS, MSD, GS, VIIV, Janssen Francois Bailly - Board Membership: ABBVIE, MSD, BMS, GILEAD; Speaking and Teaching: JANSSEN Jean-Michel Molina - Board Membership: Gilead, BMS, Janssen, merck, Abbott, boehringer; Grant/Research Support: merck; Speaking
medchemexpress and Teaching: merck, gilead, BMS The following people have nothing to disclose: Anne-Marie Taburet, Lionel Piroth, Hubert Paniez, Mélanie Simony, Valerie Furlan, Aurélie Barrail-Tran, Corine Vincent, Eric Billaud, Martine Resch, Laurence Meyer Purpose: Treatment responses to interferon-containing regimens with a protease inhibitor have historically been lower for black patients compared with white patients. The randomized phase 3 PEARL trials evaluated the safety and efficacy of the “3D” regimen of co-formulated ABT-450/ritonavir/ombitasvir and dasabuvir with or without ribavirin (RBV) in HCV genotype (GT) 1b treatment-experienced (PEARL-II) or treatment-naïve (PEARL-III) patients, and in GT1a treatment-naï;ve (PEARL-IV) patients. We assessed treatment response rates based on race or geographic location in a pooled analysis of results from the PEARL trials.