CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

1. No HCV relapses have occurred to date in patients receiving either DAA Rx. Minor adverse effects occurred in 14/29 (48%) patients, none of which resulted in HCV therapy discontinuation (pruritus, 17%, fatigue, 14%, grade 3 total bilirubin elevation, 10%). One death occurred unrelated to HCV Rx.

Conclusions: In this non-clinical trial-based study of difficult to treat HIV/HCV-infected patients, use of SOF/SMV or SOF/RBV achieved rapid HCV-RNA declines and was well tolerated. HIV co-infection should not be considered a barrier to successful HCV treatment using these combinations. Accrual and treatment of patients is ongoing. 645 Effectiveness of Sofosbuvir/Simeprevir for HIV/HCV Patients in Clinical Practice Jody Gilmore 1 ; Kenneth Lynn 1 ; Delisha Breen 1 ; StaceyTrooskin 2 ; Jihad Slim 3 ; Nancy Scangarello 3 ; Alvin Kingcade 4 ; Katie Hunyh 4 ;Vincent Lo Re 1 ; Jay R. Kostman 1 1 Perelman School of Medicine, Philadelphia, PA, US; 2 Drexel University College of Medicine, Philadelphia, PA, US; 3 St Michael’s Medical Center, Newark, NJ, US; 4 Philadelphia Health Management Corporation, Philadelphia, PA, US Background: HIV/HCV-coinfected patients have been underrepresented in clinical trials of all-oral therapies for chronic HCV genotype 1 infection. Our objective was to assess virologic responses and tolerability of sofosbuvir + simeprevir (sof/sim) in HIV/HCV-coinfected patients compared to those with HCV alone. Methods: We performed a cohort study among HCV-infected patients treated with sof/sim at 4 community-based and academic centers. The main outcome was end-of- treatment (EOT) HCV virologic response. HCV RNA, liver aminotransferases, and sof/sim discontinuations were evaluated over 12 weeks of treatment and 12 weeks of follow-up. Results were stratified by HIV status and by the presence of advanced hepatic fibrosis/cirrhosis. Results: Eighty-one patients (37 coinfected; 44 monoinfected) were treated with sof/sim between 12/2013 and 9/2014. Fifty-nine percent were African American, 61%were male, 73% had METAVIR stage 3/4 fibrosis, and 46% had prior HCV therapy (49% null or partial responders; 16% relapsers; 35% stopped due to toxicity). The most common HIV regimens in coinfected persons included raltegravir, dolutegravir, or rilpivirine with either tenofovir/emtrictabine or abacavir/lamivudine. Among HIV/HCV patients, 54% and 87% achieved an HCV RNA that was not quantifiable at 2 and 4 weeks of therapy, respectively, compared to 55% and 81% for HCV-monoinfected patients (p>0.5). Those with METAVIR stage 3/4 were equally likely to achieve HCV suppression by 4 weeks compared to those with less fibrosis regardless of HIV status (61% vs. 67% in coinfected patients, p=0.68; 56% vs. 75% in monoinfected patients, p=0.33). Overall, mean levels of alanine aminotransferase decreased from 54 U/L to 22 U/L within 2 weeks of sof/sim initiation. Of the 81 patients, only 5 (6%; 3 coinfected; 2 monoinfected) prematurely discontinued therapy (1 due to nonresponse; 1 for cutaneous reaction; 3 lost to follow-up). Among 42 patients completing 12 weeks of therapy, 37 (88%) achieved an EOT response (89% in coinfected patients; 88% in monoinfected patients, p>0.5). At the time of this analysis, 22 patients were followed for at least 4 weeks after the completion of therapy with 2 virologic relapses in monoinfected patients, 1 with METAVIR stage 3/4. Conclusions: An all-oral sof/sim regimen was effective for patients with chronic HCV genotype 1, regardless of HIV status, previous treatment response, and stage of fibrosis. Adverse events were rare, even in patients with advanced fibrosis/cirrhosis. 648 Simeprevir and Sofosbuvir Regimens for Hepatitis C: Decompensation and Serious AEs Ponni V. Perumalswami 1 ; Kian Bichoupan 1 ; Lawrence Ku 1 ; Neal M. Patel 1 ; RachanaYalamanchili 1 ;Thomas Schiano 1 ; MarkWoodward 2 ; Douglas Dieterich 1 ; Andrea D. Branch 1 1 Icahn School of Medicine at Mount Sinai, New York, NY, US; 2 George Institute for Health at the University of Oxford, Oxford, United Kingdom Background: New therapies for hepatitis C virus (HCV) were well-tolerated in registration trials; however, results in real world clinical practice can be different. We characterized hepatic decompensation and serious adverse events (SAEs) in patients receiving standard care at the Mount Sinai Medical Center. Methods: All HCV infected patients treated with regimens that contained sofosbuvir (SOF) and/or simeprevir (SMV) were included. The Cases experienced at least one of the following: hepatic decompensation, indicated by new or increased jaundice, ascites, encephalopathy, or sepsis, or another SAE. There were two cohorts: Cohort 1 included 466 patients, Cohort 2 included 43 liver transplant (LT) patients. The incidence of decompensation/SAE was calculated for each cohort. Within each cohort, a matched Case-Control study was performed to identify risk factors for decompensation/SAE. For Cohort 1, up to five Controls were selected for each Case based on treatment regimen and duration. For Cohort 2, matching was 1:2. Cases and Controls were compared using matched conditional exact analysis. Results: A total of 489 patients met the inclusion criteria: 466 in Cohort 1 (non-LT) and 43 in Cohort 2 (LT). There were 13 non-LT Cases (2.8%) and 8 LT Cases (19%), p< 0.01 for the comparison. In Cohort 1, most (62%) were on SOF/RBV, 15%were on SOF/PEG/RBV, and 23%were on SMV/SOF. Among 67 non-LT patients on PEG/RBV-free regimens, three

Oral Abstracts

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CROI 2015