CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Results: By the Abbott assay on SYNERGY, 11/17 patients had detectable (6/17 quantifiable) HCV RNA at week 4 and 5/17 patients had detectable but unquantifiable HCV RNA at EOT (Figure 1a). All patients with undetectable HCV RNA at week 4 and EOT achieved SVR12, and none with detectable HCV RNA relapsed (PPV 100 and NPV 0). By the Roche assay (Figure 1b), all patients had undetectable HCV RNA at EOT and achieved SVR 12 (PPV 100). On ERADICATE, 32/50 patients had detectable (9/50 quantifiable) HCV RNA by the Abbott assay at week 4 (Figure 1a), 31 of whom achieved SVR4 (PPV 100 and NPV 3.1). At EOT, 7/49 patients had detectable but unquantifiable HCV RNA by the Abbott assay, all of whom achieved SVR4 (PPV 100 and NPV 0). By the Roche assay (Figure 1b), all 50 patients were undetectable at EOT and 1 relapsed (PPV 98).

Poster Abstracts

Conclusions: Contrary to past experience with interferon-containing treatments, the presence of detectable HCV RNA levels at EOT is not predictive of relapse in these studies. The low negative predictive values at week 4 underscore the importance of continued therapy for patients who fail to achieve undetectable levels of HCV RNA early on during treatment because their chances of achieving SVR are still high. 690 Viral Kinetic Profiles of HCV Response to Telaprevir-Based Therapy in Patients With Hemophilia Kenneth E. Sherman 1 ; Ruian Ke 2 ; Susan D. Rouster 1 ; Alan S. Perelson 2 1 University of Cincinnati, Cincinnati, OH, US; 2 Los Alamos National Laboratory, Los Alamos, NM, US Background: The majority of patients with inherited bleeding disorders who received blood-derived factor concentrates were infected with HCV with repeated exposures to multiple HCV species. It is hypothesized that wide quasispecies representation could affect treatment responses, and that lead-in might mitigate emergent viral breakthrough. The utility of lead-in vs. DAA-based therapy in hemophiliacs was evaluated using viral dynamic modeling methods. Methods: Treatment-experienced subjects with hemophilia were treated with telaprevir/pegylated interferon alfa/weight-based ribavirin (T/P/R) and randomized to triple-drug start vs. lead-in for 1 month with P/R only. Intensive sampling of blood was performed at baseline, 3, 6, 12, 24, 48 and 72 hours after dosing, and again at days 7 and 10. Lead-in subjects underwent intensive sampling after addition of telaprevir (Week 5). Viral dynamic models were utilized for data analysis and treatment responses were assessed. Safety parameters studied included development of inhibitors to factor concentrates. Results: Seven patients with hemophilia provided informed consent. Two were screen failures (spontaneous clearance/loss to f/u prior to drug start). Among the five treated subjects, all were male, 80%were Caucasian and 1 (20%) was black, non-Hispanic. Four subjects were IL28B genotype CT, and one was CC. The mean baseline HCV RNA titer was log 6.7 IU/ml. Three subjects were randomized to lead-in followed by addition of T after four weeks, and two received standard T/P/R therapy. The lead-in subjects’ mean HCV RNA titer prior to beginning telaprevir (week 5) was 4.97. The efficacy parameter () for lead-in ranged from 0 to 0.9745 (mean= 0.514). Addition of telaprevir resulted in a mean efficacy of more than 0.999. This was comparable to subjects who started all three medications simultaneously. Overall efficacy in those with hemophilia was higher than historical non-hemophilia controls not treated with ribavirin (data not shown). Ultimately, 4/5 subjects (80%) achieved SVR. Adverse event profiles were similar to that observed in non- hemophilia cohorts. There was no evidence of factor inhibitor formation.

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CROI 2015