CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Conclusions: Our model suggests that timely treatment of HCV infection is important: Patients can progress to end-stage liver disease after HCV clearance if treatment is delayed until later stages of liver disease due to imperfect treatment responses and residual fibrosis progression in HIV-infected patients. Delaying treatment also increases the risk of HCV transmission: the average time during which patients are infectious is four times higher if patients are treated in F4 than if they are treated one month after diagnosis. 151LB Daclatasvir in CombinationWith Sofosbuvir for HIV/HCV Coinfection: ALLY-2 Study DavidWyles 1 ; Peter Ruane 2 ; Mark Sulkowski 3 ; Douglas Dieterich 4 ; Anne Luetkemeyer 5 ;Timothy Morgan 6 ; Kenneth E. Sherman 7 ; Zhaohui Liu 8 ; Stephanie Noviello 8 ; Peter Ackerman 8 1 University of California San Diego, La Jolla, CA, US; 2 Ruane Medical and Liver Health Institute, Los Angeles, CA, US; 3 Johns Hopkins University School of Medicine, Baltimore, MD, US; 4 Icahn School of Medicine at Mount Sinai, New York, NY, US; 5 University of California and San Francisco General Hospital, San Francisco, CA, US; 6 VA Long Beach Healthcare System, Long Beach, CA, US; 7 University of Cincinnati College of Medicine, Cincinnati, OH, US; 8 Bristol-Myers Squibb Co, Princeton, NJ, US Background: The pangenotypic, once-daily combination of daclatasvir (DCV) and sofosbuvir (SOF) achieves high rates of sustained virologic response (SVR) in patients with chronic HCV infection. DCV+SOF has favorable safety and drug-drug interaction profiles and a high barrier to resistance, supporting the phase 3 ALLY-2 study of DCV+SOF in patients with HIV/HCV coinfection. Methods: This randomized, open-label study enrolled HCV treatment-naive (N=151) or experienced (N=52) adults coinfected with HIV and HCV (any genotype). Naive patients were randomly assigned (2:1), with stratification by cirrhosis status and HCV GT, to receive 12 or 8 weeks of once-daily SOF 400mg + DCV 60mg (dose-adjusted for concomitant antiretrovirals: 30mg with ritonavir-boosted PIs, 90mg with NNRTIs except rilpivirine). Experienced patients received this same regimen for 12 weeks. The primary endpoint was HCV RNA < LLOQ (25 IU/mL) at posttreatment Week 12 (SVR12) in naive GT1 patients treated for 12 weeks. Results: Treatment arms were well balanced with a median age of 52 y, 87%male, and 62%white/34% black. 83%, 9%, 6%, and 2% of patients, respectively, had GT1, 2, 3, and 4 infection; median baseline HCV RNA was 6.7 log10 IU/mL; 14% had cirrhosis. The median baseline CD4 count was 565 cells/ μ L and 94% had HIV RNA <50 cp/mL. 99, 50, and 50 patients, respectively, received PI-based, NNRTI-based, or other (primarily INI-based) cART; 4 patients did not receive cART. 199/203 (98%) patients completed therapy; 2 patients discontinued early for noncompliance and 2 for incarceration. Overall, SVR12 was achieved by 97% and 98% of naive and experienced patients, respectively, after 12 weeks of therapy, and by 76% of naive patients after 8 weeks (Table). Among patients treated for 12 weeks, SVR12 rates were similar regardless of prior treatment experience, HCV GT or GT1 subtype, cirrhosis status, concurrent cART regimen, or race. There were no virologic breakthroughs; 2/153 patients (1%) in the 12-week group and 10/50 (20%) in the 8-week group had posttreatment relapse. There were no treatment-related serious AE or AE leading to discontinuation. Treatment-emergent grade 3/4 lab abnormalities included increases in INR (2 patients), AST (1), total bilirubin (8, all received ATV/r), and lipase (7, all transient without pancreatitis).

Oral Abstracts

Conclusions: DCV+SOF once daily for 12 weeks achieved SVR12 in 97% of patients coinfected with HIV and HCV GT1, 2, 3, or 4, and was safe and well-tolerated. 152LB Ledipasvir/Sofosbuvir for 12Weeks in Patients CoinfectedWith HCV and HIV-1 Susanna Naggie 1 ; Curtis Cooper 2 ; Michael S. Saag 3 ; Jenny C.Yang 4 ; Luisa M. Stamm 4 ; Phillip S. Pang 4 ; John McHutchison 4 ; Douglas Dieterich 5 ; Mark Sulkowski 6 On behalf of the ION-4 StudyTeam 1 Duke Clinical Research Institute, Durham, NC, US; 2 University of Ottawa, Ottawa, Canada; 3 University of Alabama at Birmingham, Birmingham, AL, US; 4 Gilead Sciences, Inc, Foster City, CA, US; 5 Mount Sinai Health System, New York, NY, US; 6 Johns Hopkins University School of Medicine, Baltimore, MD, US Background: Historically HIV co-infection was considered a negative predictor of HCV response to treatment with interferon/ribavirin (IFN/RBV). For sofosbuvir-based regimens, HIV/HCV patients have achieved similar sustained virologic response (SVR) rates as HCV monoinfected patients. We evaluated the safety and efficacy of the IFN-free, RBV-free, single tablet regimen of ledipasvir/sofosbuvir (LDV/SOF) in HCV genotype 1 or 4 patients co-infected with HIV-1 in the Phase 3 ION-4 study. Methods: HCV treatment naïve and experienced HIV co-infected patients on stable, approved antiretroviral (ARV) regimens were enrolled and received LDV/SOF (90mg/400mg) once daily for 12 weeks. Patients with compensated cirrhosis were eligible. Permitted concomitant ARVs included tenofovir and emtricitabine (TDF+FTC) with raltegravir (RAL), efavirenz (EFV) or rilpivirine (RPV). Safety evaluations included adverse event (AE) and standard laboratory parameter monitoring in addition to enhanced renal toxicity monitoring, CD4 count and HIV-1 RNA levels. The primary efficacy endpoint was SVR12. Results: 335 patients with GT1a (75%), GT1b (23%) and GT4 (2%) were enrolled; 82%were male, 61%were white, mean age was 52 (range 26-72), mean baseline HCV RNA was 6.7 log 10 IU/mL (range 4.1-7.8), median baseline CD4 count was 662 cells/uL (Q1, Q3=469, 823), 20% had cirrhosis, 24%were IL28B CC genotype and 55% had not responded to prior HCV treatment. Patients were taking EFV (48%) or RAL (44%) or RPV (9%). The table shows SVR12 by ARV regimen. Overall, the SVR12 rate was 96% (320/335); 2 patients had on-treatment virologic failure likely due to non-compliance and 10 had virologic relapse after discontinuing treatment. SVR12 was similar among non-cirrhotic (96%) and cirrhotic (94%) patients and also among treatment naïve (94%) and treatment experienced (97%) patients. No patient had confirmed HIV virologic rebound (HIV-1 RNA ≥ 400 copies/mL). No patients discontinued study drug due to an AE. AEs occurring in ≥ 10% of patients were headache (25%), fatigue (21%) and diarrhea (11%). No significant lab abnormalities were observed.

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CROI 2015