CROI 2015 Program and Abstracts

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Poster Abstracts

647 Real-World Data on HIV-Positive Patients With HCV TreatedWith Sofosbuvir and/or Simeprevir David Del Bello 1 ; Kian Bichoupan 1 ; Calley Levine 1 ; Agnes Cha 2 ; David Perlman 1 ; Nadim H. Salomon 1 ; Donald Kotler 1 ; Daniel Fierer 1 ; Douglas Dieterich 1 ; Andrea Branch 1 1 Mount Sinai Health System, New York City, NY, US; 2 Brooklyn Medical Center, New York City, NY, US Background: We are investigating the effectiveness of simeprevir (SMV) and sofosbuvir (SOF) in a real-world setting for patients with HIV/HCV co-infection. Methods: Data on 80 HIV/HCV co-infected patients who initiated therapy between 12/2013 and 8/2014 were analyzed. Baseline and week-2 on-treatment data are reported. Week-4 and Week-12 post end-of-treatment responses were examined to determine the sustained virologic response (SVR) rates for patients who have completed therapy. Advanced fibrosis/cirrhosis was defined as a FIB-4 score ≥ 3.25. By 2/2015, SVR4 data will be available for all 80 patients. Data will also be available for additional co-infected patients (enrollment is on-going) and for a comparison cohort of patients with HCV mono-infection. Results: Median age of the 80 HIV/HCV co-infected patients was 57 yr (range, 25-73 yr), 84%were male, 63%were white, 25%were black, and 38%were Hispanic. Nearly half (41%) were naïve to HCV treatment. Comorbidities were common: 50% had hypertension, 38% had depression, 16% had diabetes, 51% had advanced fibrosis/cirrhosis, and 8% had HCC. The baseline median HCV VL was 6.31 IU/mL (IQR: 5.9-6.7 IU/mL), platelet count was 135 x10 3 / m L (IQR: 97-195 x10 3 / m L), albumin was 3.9 g/dL (IQR: 3.6-4.2 g/dL), total bilirubin was 0.6 mg/dL (IQR: 0.5-1.0 mg/dL), and the CD4 count of the 54 patients with these data was 487 (IQR: 325-620); HIV VL was undetectable in 46/54 (85%). All but four patients were on HAART. Of 67 patients with genotype (gt) 1, 33 (39%) were on SOF/ribavirin (RBV), 15 (22%) were on SMV/SOF/RBV, and 19 (28%) were on SMV/SOF; 15 (22%) patients changed HAART to accommodate SMV. All 13 patients with gt 2 or 3 HCV were on SOF/RBV. At week-2, 66% of patients had data available. Of 26 gt 1 patients on SMV, HCV RNA was undetectable in 9 (35%). Of 27 patients on SOF/RBV, HCV RNA was undetectable in five (20%). SVR4 data are available for 28 gt 1 patients:15/15 (100%) on a SMV regimen achieved SVR4, as did 7/13 (54%) on SOF/RBV. SVR12 data are available for seven patients on SMV/SOF, all achieved SVR12. Only one gt 1 patient on SOF/RBV achieved SVR12. Table. Characteristics and SVR 4 rates stratified by genotype Conclusions: SMV and SOF are important and highly effective DAAs for HIV/HCV co-infected patients, a group that was notoriously difficult to treat with interferon. SVR4 was achieved by all 15 patients treated with SMV/SOF (with or without RBV) who have reached the 4-week post end of treatment time point (DA031095, DK090317). 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 decompensated/experienced an SAE (4%). In Cohort 2, all were on SOF/RBV. Treatment was discontinued in 4/13 (31%) of non-LT Cases and in 2/8 (25%) of LT Cases. Similar to registration trials, liver decompensation/SAE lead to treatment discontinuation in 1% (5/466) of the entire non-LT Cohort and in 5% (2/43) of the entire LT Cohort. Among non-LT patients, risk factors for SAE/decompensation included low baseline albumin, high INR, and high total bilirubin. In LT patients, lower hemoglobin, eGFR, ALT, AFP and higher serum creatinine were risk factors for SAE/decompensation. Conclusions: This study identified subgroups of non-LT and LT patients who may require more intensive monitoring and additional interventions to successfully complete SMV- and SOF-based treatment regimens. Patients with reduced hepatic biosynthetic function and LT patients were especially vulnerable to serious AEs and decompensation (DA031095, DK090317). 649 Successful HCV Treatment With Direct Acting Antivirals in HIV/HCV Patients Jennifer L. Grant 1 ;Valentina Stosor 1 ; Frank J. Palella 1 ; Richard M. Green 1 ; GuajiraThomas 1 ; DonnaV. McGregor 1 ; Milena M. McLaughlin 2 ; Sudhir Penugonda 1 ; Michael Angarone 1 ; Claudia Hawkins 1 1 Northwestern University, Feinberg School of Medicine, Chicago, IL, US; 2 Midwestern University, Chicago, IL, US Background: IFN-free combinations of direct acting antivirals (DAA) are associated with high cure rates in HCV-infected patients. The SOF/SMV combination has not yet been studied in HIV/HCV co-infected persons. We evaluated outcomes in HIV/HCV patients receiving IFN-free DAA therapy in a large urban clinic in Chicago. Methods: In a prospective observational analysis of HCV treatment experienced and treatment naïve co-infected adults (>18 years) enrolled in the Northwestern University Viral Hepatitis Registry from Jan-Sep 2014, we evaluated the efficacy and safety of SOF/RBV (24 weeks) and SOF/SMV (12 weeks). HCV virologic responses were assessed at week 2 and then monthly during therapy (Rx) and 4 and 12 weeks after completion of Rx (SVR 4 and 12). HCV relapse was defined as a detectable HCV-RNA (lower limit of detection 15 IU/mL) at 4 or 12 weeks after Rx completion. We used chi-square and students’ T-test (SPSS version 22.0, Armonk, NY; IBM Corp.) for between group comparisons. Results: We evaluated 42 HIV/HCV patients [median age 53 years (IQR 47, 60); 81%male; 50% Caucasian; median CD4+ T cell count 522 cells/mm 3 (IQR 292, 660)] for HCV Rx. Risk factors for HCV included MSM (41%) and IDU (41%). Rx was initiated in 32/42 (76%) patients with either SOF/SMV (28, 87.5%) or SOF/RBV (4, 12.5%). Males (85.3% vs. 25% (females); p<0.01) and patients with higher mean FibroSure™ scores (0.70 vs. 0.46; p=0.047) were more likely to receive HCV Rx. There were 21 (66%) with genotype (GT) 1a, 8 (25%) with GT 1b, and 1 each (3%) with GT 2, 3 and undifferentiated. 14/32 (44%) had previously received either PEG/RBV (12/14) or PEG/RBV+BOC (2/14). Median pre-Rx HCV-RNA was 1,384,532 copies/ml (IQR 798,853, 3,772,827) and 23/32 (72%) had advanced liver fibrosis (> F3). All patients received indicated ART. HCV-RNA responses are shown in Figure

Poster Abstracts

406

CROI 2015