CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

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). 651 Majority of HIV/HCV Patients Need to Switch ART to Accommodate Simeprevir Rebecca Cope 1 ; Aaron Pickering 2 ;Thomas Glowa 1 ; Samantha Faulds 1 ; PeterVeldkamp 1 ; Ramakrishna Prasad 1 1 University of Pittsburgh, Pittsburgh, PA, US; 2 University of Maryland, Glen Burnie, MD, US Background: The impact of drug-drug interactions (DDIs) between Simeprevir (SMV) and antiretrovirals (ART) in limiting HCV treatment among HIV/HCV co-infected individuals in clinical practice settings is unknown. We determined: a) the need to switch antiretroviral therapy (ART) prior to initiation of SMV; and b) the feasibility of switching ART to allow SMV use. We hypothesized that the majority of co-infected patients will require an ART switch and a safe and effective ART switch will be challenging in patients on a protease inhibitor (PI) based ART regimen. Methods: A retrospective chart review was conducted at the University of Pittsburgh Medical Center’s HIV/AIDS Program from June-August 2014. All patients with HIV and chronic HCV with a visit in the past 18 months were included. After collection of baseline characteristics, significant interactions between SMV and ART were identified based on available literature. If DDIs limited use of SMV, previous HIV genotype reports were reviewed to determine the feasibility of a safe and effective ART switch. Results: Of 133 patients, 71%were male, 54% African American, 23%met criteria for advanced liver disease, 86% had HCV genotype 1, and 94%were currently on ART. The distribution of regimens was: ritonavir-boosted PI (PI/r) (38%); efavirenz (34%); raltegravir (11%); rilpivirine (6%); elvitegravir/cobicistat (1%); and other regimens including dolutegravir (4%). An ART switch to allow use of SMV was required in 103 (77%), most frequently for patients on efavirenz or a PI/r. For 47 (46%), a straightforward substitution could be made. For the remaining patients, a switch following HIV expert opinion was viable in 40 (39%), but no switch was possible in 16 (15%) due to archived HIV drug resistance mutations. Notably, for more than 30% of patients on a PI, an ART switch was not feasible. Conclusions: The majority of HIV/HCV co-infected patients will require ART switch prior to use of SMV. Additionally, for nearly a third of patients on a PI, an ART switch may not be feasible. These findings are significant to real world clinical practice settings and highlight the complexity of using Interferon-free DAAs in this population and add further stress to an already burdened HIV care delivery system. 644 Sofosubuvir, Simeprevir, +/- Ribavirin in HCV Protease Inhibitor-Experienced Patients Kristen M. Marks ; Ethan M.Weinberg; Sonal Kumar; Carrie Down;Ype P. de Jong; Leah A. Burke; Mary C. Olson; Ira M. Jacobson Weill Cornell Medical College, New York, NY, US Background: Little data exists on use of HCV protease inhibitors (PIs) as part of a treatment (Rx) regimen for PI-experienced G1 patients (pts). Since polymorphisms associated with PI-resistance decrease to baseline levels over time in most studied subjects, sofosbuvir (SOF) + simeprevir (SMV) +/- ribavirin (RBV) represents a potential retreatment option for PI-experienced pts. Methods: We compiled a retrospective cohort of HCV PI-experienced G1 pts treated with SOF+SMV+/-RBV at our center. Baseline factors including prior regimen & Rx response, fibrosis stage, HCV genotype & resistance testing (population-based) data, viral RNA levels, demographic data as well as on Rx response, SVR4, and SVR12 were collected and reported. Results: In 2014, 15 pts with genotype 1 and prior PI experience initiated Rx because of clinical need with 12 wks SOF+SMV with (10) or without (5) RBV . Median age was 61 yrs (range 26-73), baseline HCV RNA 6.5 log IU/ml (5.5-7.0 log), 12 were male, and 10 had cirrhosis. PI Rx occurred 26 (5-85) months prior and included telaprevir (10), boceprevir (3), ABT 450/r (1), GS9451 (1) as part of Rx regimen with 11 nonresponders, 1 relapser, and 3 intolerant of Rx. All had genotype and resistance testing performed prior to SOF+SMV+/- RBV. Of the 9 G1a pts, Q80K was detected in 4, Q80L in1. Of the 6 G1b pts, V36I and T54S were detected in 1 pt each. No other mutations associated with PI resistance were detected. Responses to SOF+SMV+/-RBV are shown in the table.

Oral Abstracts

*The pt with relapse received SOF+SMV+RBV, had G1b, cirrhosis and a prior history of telaprevir-based Rx completed 14 months prior, and had no known mutations associated with resistance. Conclusions: Conclusion: SOF+SMV+/-RBV treatment may be appropriate for carefully selected PI-experienced G1 pts including those with cirrhosis. Further study is needed to confirm these findings. 746 Cumulative HIV Care Measures Highly AssociatedWith Acute Myocardial Infarction Jorge L. Salinas 1 ; ChristopherT. Rentsch 2 ;Vincent C. Marconi 1 ; JanetTate 3 ; Adeel A. Butt 4 ; Matthew S. Freiberg 4 ; Matthew B. Goetz 5 ; Maria Rodriguez-Barradas 6 ; Amy Justice 3 ; David Rimland 1 1 Emory University, Atlanta, GA, US; 2 Atlanta VA Hospital, Decatur, GA, US; 3 Yale University, New Haven, CT, US; 4 University of Pittsburgh, Pittsburgh, PA, US; 5 David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, US; 6 Baylor College of Medicine, Houston, TX, US Background: After accounting for established risk factors, people living with HIV (PLWHIV) have a 50-75% greater risk of acute myocardial infarction (AMI) than uninfected individuals. Several underlying causes for this association have been suggested including ongoing chronic inflammation, immune suppression, and a greater burden of anemia, renal disease, liver disease, and hepatitis C infection. While many of these factors have been studied in a cross-sectional manner, few have considered the association of cumulative HIV care measures with AMI among PLWHIV. We hypothesized that measuring these factors in a cumulative way would be associated with AMI incidence.

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CROI 2015