CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: T/P/R was highly effective in HCV clearance among hemophilic subjects. There was no evidence that lead-in provided benefit in terms of response efficacy, but addition of telaprevir led to rapid viral decline. These data support DAA-based therapy in those with inherited bleeding disorders. 691 Hematologic Analysis of ABT-450/r/Ombitasvir and Dasabuvir + RBV in TURQUOISE-I Robert S. Brown 1 ; DavidWyles 2 ; Jihad Slim 3 ; Peter J. Ruane 4 ; Barbara McGovern 5 ; RogerTrinh 5 ;Yiran Hu 5 ; Joseph J. Eron 6 1 Johns Hopkins University, Baltimore, MD, US; 2 University of California San Diego, La Jolla, CA, US; 3 St Michael’s Medical Center, Newark, NJ, US; 4 Peter J. Ruane MD Inc, Los Angeles, CA, US; 5 AbbVie, Inc, North Chicago, IL, US; 6 University of North Carolina, Chapel Hill, NC, US Background: Combination therapy of ribavirin (RBV)+peginterferon (pegIFN) with protease inhibitors for the treatment of HCV is commonly associated with hematologic abnormalities. We sought to analyze immune parameters in patients co-infected with HCV and HIV-1 treated with the 3 direct-acting antiviral (3D) regimen of co-formulated ABT-450 (identified by AbbVie and Enanta)/ritonavir/ombitasvir and dasabuvir given with weight-based RBV. SVR 4 rates of 93.5 and 96.9%were observed with 12- and 24-weeks of 3D+RBV therapy in patients co-infected with HCV/HIV-1. Methods: TURQUOISE-I is a 2-part ongoing, randomized, open-label Phase 2/3 study evaluating the safety and efficacy of 3D+RBV for 12- or 24-weeks in HCV genotype 1/ HIV-1 co-infected treatment-naïve or pegIFN/RBV -experienced adults with and without cirrhosis. Laboratory values were assessed at every study visit and post-treatment visit. Treatment-emergent adverse events (AEs) were assessed from the first dose until 30 days after the last dose for any patient who received at least one dose of study drugs. Results: Hemoglobin decreases were comparable between 12- and 24-week treatment arms (Table). Treatment-emergent anemia was reported in 1 patient in the 12-week arm and in 3 patients in the 24-week arm. RBV dose modification due to decreased hemoglobin occurred in 6 patients (4 in the 12-week arm; 2 in the 24-week arm); all achieved SVR 12 . No patient had a post-baseline Grade 3 or 4 decrease in hemoglobin. No patient used erythropoietin or received a blood transfusion. Mean absolute CD4+ T cell counts and lymphocytes decreased during treatment and increased to above baseline levels by post-treatment week 12 (Table). CD4 percentages remained stable over time in both treatment arms. No patient had clinically significant abnormalities in platelet or white blood cell counts. Among the 3 patients who experienced a CD4+ T cell count <200 cells/mm 3 or CD4+ percentage <14% during treatment, none experienced an AIDS-associated opportunistic infection.

Conclusions: Among HCV/HIV-1 co-infected treatment-naïve and -experienced patients, anemia events were infrequent with 3D+RBV treatment and did not affect treatment outcomes. Transient declines in absolute CD4+ T cells paralleled changes in total lymphocyte count, which is consistent with known hematologic effects of RBV. 692 Effect of HIV Coinfection on Adherence to a 12-Week Regimen of HCV Therapy With Ledipasvir/Sofosbuvir

Poster Abstracts

Kerry S. Townsend 1 ;Tess L. Petersen 2 ; Lori A. Gordon 2 ; Amy Nelson 1 ; Cassie Seamon 2 ; Chloe Gross 3 ; Anu Osinusi 2 ; Michael A. Polis 1 ; Henry Masur 2 ; Shyam Kottilil 1 1 National Institute of Allergy and Infectious Diseases, Bethesda, MD, US; 2 National Institutes of Health, Bethesda, MD, US; 3 Leidos Biomedical 18 Research Inc, Frederick, MD, US

Background: The treatment of hepatitis C virus (HCV) infection is rapidly evolving to interferon (IFN) and ribavirin (RBV) free treatment with directly acting antiviral agents (DAAs). The impact of DAAs on HCV treatment adherence in HIV/HCV co-infected populations has not been extensively evaluated. We compared adherence rates of the IFN and RBV free DAA regimen of ledipasvir/sofosbuvir (LDV/SOF) between HCV mono-infected and HIV/HCV co-infected patients. Methods: Participants were representative of the urban Washington D.C. cohort and were HCV treatment naïve, genotype 1 study subjects from two National Institute of Allergy & Infectious Diseases (NIAID) phase 2 clinical trials (Synergy A: HCV mono-infected participants, n=20, and Eradicate: HIV/HCV co-infected participants, antiretroviral (ARV) naïve, n=13, on combination ARV therapy, n=37). Patients were treated with LDV (90 mg) + SOF (400 mg) as a fixed dose combination once daily for twelve weeks. Adherence was measured using three tools: MEMS (Medication Event Monitoring System) caps, pill counts, and patient report. Adherence over time was compared using Wilcoxon T test. Analyses were performed using PRISM 6.0 (Graphpad). Results: Patients enrolled were predominately African American (83%) and male (73%), with a median age of 59 years. Patients in all three-treatment groups had prompt viral load decline associated with high adherence rates. Only twelve out of the sixty patients (20%) missed 4 or more pills. However, patient adherence significantly decreased from baseline - week 4 compared to week 8 - 12 in all three groups [HCV mono-infected (p=0.02), HIV/HCV ARV naive (p=0.01), and HIV/HCV ARV treated patients (p=0.01)].

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CROI 2015