CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Poster and Themed Discussion Abstracts

567 HCV REINFECTION AFTER SUCCESSFUL DAA TREATMENT: A GECCO ANALYSIS Patrick Ingiliz 1 , Stefan Christensen 2 , Florian Berger 3 , Torben Kimhofer 4 , Knud Schewe 5 , Christoph Boesecke 6 , Dietrich Hueppe 7 , Julian Schulze zur Wiesch 8 , Thomas Lutz 9 , Stefan Mauss 3 1 Cntr for Infectiology, Berlin, Germany, 2 CIM Infectious Diseases, Münster, Germany, 3 Cntr for HIV and Hepatogastroenterology, Duesseldorf, Germany, 4 Imperial Coll London, London, UK, 5 dagnae e.V., Berlin, Germany, 6 Univ Hosp Bonn, Bonn, Germany, 7 Gastroenterology Practice, Herne, Germany, 8 Univ Med Cntr, Hamburg-Eppendorf, Germany, Hamburg, Germany, 9 Infektiologikum, Frankfurt, Germany Background: Reinfection with the hepatitis C virus has been described in patients with ongoing risk behaviour for HCV acquisition after spontaneous clearance or succesful treatment. The highest incidences have been described in active intravenous drug users (IDUs) and in HIV-positive men who have sex with men (MSM). Among the latter, users of intravenous and non-intravenous drugs (mainly methamphetamine) for sexual enhancement (Chemsex) have been identified as a main risk group for HCV acquisition. In HIV infected MSM in Western Europe in the interferon era, 25% have been found to be reinfected with HCV three years after HCV cure. The frequency of HCV reinfections after treatment with direct-acting antivirals (DAA) is not known. Here, we analysed the reinfection rate in the GECCO cohort. Methods: The German hepatitis C cohort (GECCO) consists of treatment data on all directly acting antiviral agents from HCV mono- and HIV-HCV coinfected patients from nine centers since February 2014. Reinfection was defined as an detectable HCV RNA in a patient that had an undetectable HCV RNA 12 weeks after the end of treatment (SVR12), or with an HCV genotype switch. Results: Up to May 2016, 1636 patients have been cured with DAA combinations within the GECCO cohort. Overall, 16 patients (1%) have been identified with an HCV reinfection. All patients were male, the median age was 46 years (IQR 38-52), and 13/16 (81%) were HIV-HCV coinfected. The three HCV mono-reinfections appeared in intravenous drug users (IDU), while all 13 coinfected patients were MSM. Six out of the 13 (46%) MSM declared to have occasional intravenous recreational drug use. The median time from end-of-DAA- treatment to reinfection was 35 weeks (range 5-112). In 9 patients (69%) a genotype switch occured. The reinfection rate in IDUs was 0.5% (3/586), and 0.8% in those on opiate substution treatment (3/355). In MSM, however, it was 7.4% (13/175) (p<0.001). Conclusion: Within the multicentric GECCO cohort, reinfection remains a rare event. Obviously, subgroups with ongoing risk behaviour remain at risk for HCV reinfection, with MSM being more affected than IDUS. In HIV-infected MSM, similar reinfection rates as in the pre-DAA era are observed, again highlighting this subgroup as a target population for close monitoring and specific behavioural interventions. 568LB LEDIPASVIR/SOFOSBUVIR±RIBAVIRIN IN HCV AND HCV/HIV PRIOR SOF-BASED VIROLOGIC FAILURES Edward Tam 1 , Robert S. Brown, Jr 2 , Sanjaya Satapathy 3 , Gregory Camus 4 , Amanda Copans 4 , Lorenzo Rossaro 4 , Willliam D. Guyer 4 , Richard Haubrich 4 , Minhee Kang 5 , Annie Luetkemeyer 6 1 LAIR Cntr, Vancouver, Canada, 2 Weill Cornell Med, New York, NY, USA, 3 Univ of Tennessee, Memphis, TN, USA, 4 Gilead Scis, Inc, Foster City, CA, USA, 5 Harvard Univ, Boston, MA, USA, 6 Univ of California San Francisco, San Francisco, CA Background: Current AASLD guidance, based on limited data and non-randomized studies, recommends 12-24 weeks (wks) of ledipasvir/sofosbuvir (LDV/SOF)+ribavirin (RBV) for retreatment of patients who failed prior SOF-based therapy. Methods: Two prospective randomized studies evaluated the efficacy, safety, and duration of LDV/SOF±RBV for treatment of HCV mono- and HCV/HIV co-infected patients who relapsed after simeprevir (SMV)+SOF±RBV or SOF+RBV±pegylated interferon (PEG) regimens. Study 1 (GS-US-337-1746) enrolled 87 genotype (GT)1 and GT4 adult patients. Non- cirrhotics were randomized to Arm 1: LDV/SOF 12 wks or Arm 2: LDV/SOF+RBV 12 wks, and compensated cirrhotics to Arm 3: LDV/SOF+RBV 12 wks or Arm 4: LDV/SOF 24 wks. Study 2 (ACTG A5348) randomized 7 GT1 adults with HCV/HIV co-infection with controlled HIV to Arm A: LDV/SOF+RBV 12 wks or Arm B: LDV/SOF 24 wks. Both studies excluded NS5A- experienced patients, with sustained virologic response (SVR12) as the primary endpoint. NS5A and NS5B resistance associated substitutions (RASs) were analyzed at baseline and, if applicable, at time of virologic failure using deep-sequencing at a 15% cutoff. Results: Five patients terminated the study prior to starting study drug. All remaining 82 patients in Study 1 and all 7 in Study 2 completed treatment. In Study 1, 69/82 (84%) patients have currently completed 12 week post-treatment follow up: 73%were male, 28% black, mean age 58 years, 52% cirrhotic, 90% GT1 (GT1a=65%), and 94% IL28B non-CC. Overall SVR12 was 87% (range 76-100%, see table). Eight patients experienced virologic failure (relapse) and one was lost to follow up after attaining SVR4. 6/8 with RAS data available developed treatment emergent NS5A RASs. Nine patients (13%) had baseline NS5A RASs and of those 8/9 (89%) achieved SVR12. Of those without baseline NS5A RASs, 52/60 (87%) achieved SVR12. 80% experienced an adverse event (AE); 1 serious AE not related to study drug. In Study 2, 5/7 were male, mean age 55, 1 cirrhotic, 5/7 GT1a. 6/7 have data available at 4 wks follow up, of whom all attained SVR4 with no SAEs or premature discontinuations. Conclusion: In this SOF-experienced NS5A-naive population, high SVR rates were achieved with LDV/SOF±RBV for 12 or 24 wks, including patients with HCV/HIV co-infection. Highest SVR rates were observed with 12 wks LDV/SOF+RBV in non-cirrhotics and 24 wks LDV/SOF in cirrhotics, suggesting RBV may not be needed when duration is extended in cirrhotics. Baseline RASs did not impact treatment outcome.

CROI 2017 239