CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Session O-12 Oral Abstracts

Room 6AB

10:00 am– 12:00 pm Curing HCV: Mission Accomplished 145 The Burden of Liver Disease Among Persons With Hepatitis C in the United States

Monina Klevens 1 ; Xiaohua Huang 2 ; Anthony E.Yeo 2 ; Mouneer Odeh 2 ; Rick L. Pesano 2 ; JohnW.Ward 1 1 US Centers for Disease Control and Prevention, Atlanta, GA, US; 2 Quest Diagnostics, Madison, NJ, US Background: In the United States, the CDC recommends one-time hepatitis C virus (HCV) antibody testing for persons born from 1945-1965 due to the higher seroprevalence of HCV infection in this group. However, the burden of liver disease among the infected population has not been described. Methods: Data were from Quest Diagnostics, a CDC partner, which conducts routine HCV tests in all states. For this analysis, all test data were anonymized and de-duplicated at the person level. The sample included all tests for which a first positive HCV RNA result was known for a given year from 2010-2013. Values for AST, platelet count and ALT, were combined with age to calculate FIB-4, a non-invasive scoring system indicative of liver fibrosis. Test data were then examined by year and stage of fibrosis. Results: During 2010-2013, a total of 273,143 persons had a first positive HCV-RNA test result and known date of birth. Of these, 186,416 (68.2%) were born from 1945-1965. For all years combined, most persons in the birth cohort had moderate fibrosis (42.3%) followed by severe fibrosis (28.7%) and cirrhosis (22.7%). Almost no variation was found over the four-year period by stage of FIB-4 (Table). In 2013, 53.1% of persons born from 1945-1965 had severe fibrosis or cirrhosis; this was higher than among persons born after 1965 (12.4%) but lower than among persons born before 1945 (79.7%). Number and percent+ of persons born during 1945-1965 with a first positive HCV-RNA test result* by year and stage of fibrosis

+ Percentage excluding unknown/missing *Not known to have a previous positive RNA test ^ Includes persons with ≥ 1 parameter missing

Conclusions: Alarmingly, about one-half of HCV-infected persons born from 1945-1965 had severe fibrosis or cirrhosis as evidenced by FIB-4 scoring. No decreases were observed in this proportion over time. Persons with this stage of severe HCV-related liver disease are a high priority for treatment. Improved birth cohort screening for HCV and linkage to recommended care and treatment are urgently needed to prevent complications. 146 High Efficacy of Daclatasvir/Asunaprevir/PR in HIV/HCV1-4 Null Responders (ANRS HC30) Lionel Piroth 1 ; Hubert Paniez 2 ; CorineVincent 2 ; Karine Lacombe 3 ; David Rey 4 ; Didier Neau 5 ; Jacques Izopet 6 ; Alpha Diallo 7 ; Laurence Meyer 2 ; Jean-Michel Molina 8 1 CHU Dijon, Dijon, France; 2 Inserm, Paris, France; 3 Hôpital Saint-Antoine, Paris, France; 4 Strasbourg University Hospital, Strasbourg, France; 5 CHU, Bordeaux, France; 6 CHU, Toulouse, France; 7 Inserm-ANRS, Paris, France; 8 CHU Saint Louis, Paris, France Background: Few direct anti-HCV agents (DAAs) have been studied in difficult to treat HIV co-infected patients, in particular null responder and cirrhotic. Daclatasvir and Asunaprevir combined with pegylated interferon-ribavirin (PR) have shown promising results in HCV mono-infected patients. Methods: An open label, single arm, phase 2 study (ANRS HC30 QUADRIH) in HIV/HCV genotype (GT) 1 or 4 co-infected patients, null responders to prior pegylated interferon- ribavirin (PR) standard bitherapy. Patients had to have plasma HIV RNA levels < 400 cp/ml and received a 4-week lead-in phase with PR, followed by 24 weeks of asunaprevir (100mg bid), daclatasvir (60 mg qd), and PR. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12) using ITT analysis. Results: Seventy-five patients (59 men/16 women) were included, median age 50 (IQR: 48 - 53) years, 27 (36%) cirrhotic. All were on a raltegravir-based regimen, 92%with baseline (BL) plasma HIV RNA level <50cp/ml, with BL median CD4 count 748 (481 - 930)/mm 3 . BL plasma HCV viral load was 6.1 (5.8 - 6.6) log10 UI/mL. The global SVR12 rate was 96.0% (72/75; 95%CI: 91.6%-100%). SVR12 was 92.6% (25/27; 82.7%-100%) in cirrhotic patients, 94.6% (35/37; 87.3%-100%) in GT1and 97.4% (37/38; 92.3%-100%) in GT 4. Eleven patients (15%) reached HCV undetectability at W5, 28 (37%) at W6, and 45 (60%) at W8. In the 51 patients experiencing less than a 1 log 10 IU/ml HCV RNA decrease during the lead-in phase, SVR12 was 94.1%. Six patients (8%) prematurely stopped HCV therapy, 2 due to virological breakthrough, and 4 to adverse events (one lung cancer, 3 infections). One of these patients (with BL platelets<150,000/mm 3 and BL albumin<35g/l) died frommultivisceral failure. Overall, 35 serious adverse events occurred in 21 (28%) patients (9 cirrhotic and 12 non cirrhotic, p=0. 44), including hematological (15%, mainly anemia and neutropenia), gastrointestinal (5%), psychiatric events (5%, mainly insomnia), and infections (5%). Conclusions: In HIV/HCV GT1/4 null responders, one third of whom had cirrhosis, a 24-week regimen combining daclatasvir/asunaprevir/PR was associated with a very high SVR12 rate. The safety profile was acceptable, even though cirrhotic patients with low albumin and platelets levels should be closely monitored This combination represents a new treatment option in this highly difficult to treat population. 147 High SVR Regardless of Time to SuppressionWith ABT-450/r/Ombitasvir & Dasabuvir+RBV DavidWyles 1 ; Joseph J. Eron 2 ; RogerTrinh 3 ; Jay Lalezari 4 ; ChiaWang 5 ; Laveeza Bhatti 6 ; Peter Gulick 7 ; Barbara McGovern 3 ; Linda Fredrick 3 ; Mark Sulkowski 8 1 University of California San Diego, La Jolla, CA, US; 2 University of North Carolina, Chapel Hill, NC, US; 3 Abbvie Inc, North Chicago, IL, US; 4 Quest Clinical Research, San Francisco, CA, US; 5 Virginia Mason Medical Center, Seattle, WA, US; 6 AIDS Healthcare Foundation, Los Angeles, CA, US; 7 Michigan State University, East Lansing, MI, US; 8 Johns Hopkins University, Baltimore, MD, US Background: SVR12 rates >90% have been achieved with the interferon-free 3 direct-acting antiviral regimen (3D) of co-formulated ABT-450 (identified by AbbVie and Enanta)/ ritonavir/ombitasvir with dasabuvir +/- RBV in HCV genotype (GT) 1 mono-infected patients. We assessed HCV RNA viral suppression over time in HCV/HIV-1 co-infected patients treated with 3D+RBV and in mono-infected patients treated with 3D+/-RBV. Methods: Data from the pooled population of HCV GT-1 mono-infected patients from six phase 3 trials of 3D+/-RBV for 12 weeks or 24 weeks (N=2053) and the HCV/HIV-1 co- infected patients from the Phase 2 TURQUOISE-I trial of 3D+RBV for 12 or 24 weeks (N=63) were included. Patients who experienced non-virologic failure were excluded from the

Oral Abstracts

168

CROI 2015