CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Methods: This is a retrospective analysis of all patients included in two prospective cohorts (clinicaltrials.gov ID NCT02057003 and NCT02333292) who harbored cirrhosis at treatment initiation and who completed a course of therapy against HCV infection including at least one DAA. Cirrhosis was defined as a LS equal to or above 12.5 kPa. Results: A total of 322 patients were included, 188 (58.4%) were HIV-coinfected and 211 (65.5%) individuals received an interferon-free regimen. The overall median liver stiffness (interquartile range) at baseline was 24 (17.3-35.1) kPa. SVR twelve weeks after the scheduled end-of-therapy (SVR12) was achieved by 101 (91%) subjects treated with interferon- free regimens and by 118 (55.9%) subjects treated with interferon-based combinations. The rates of patients who achieved SVR12 according to baseline LS and treatment regimen in an intention-to-treat analysis are shown in Figure 1. In an on-treatment analysis, 3/105 (2.9%) patients with a LS below 21 kPa versus 10/106 (9.4%) with a LS equal or above 21 kPa relapsed (p=0.047). In a multivariate analysis adjusted for age, sex, response to previous therapy, HIV coinfection, HCV genotype and baseline viral load, a baseline LS equal or above 40 kPa was the only factor that showed a trend to a significant association with SVR12 [adjusted odds ratio (95% confidence interval): 0.457 (0.187-1.119); p=0.086] in the subpopulation treated with interferon-based therapy. Conclusions: Cirrhotic patients with higher LS respond more poorly to DAA-based therapy against chronic HCV infection in clinical practice, at least when interferon-based regimens are used. This should be considered when designing clinical trials, which should stratify cirrhotic patients according to their level of baseline LS.

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Success of Direct-Acting Antivirals for Hepatitis C in an Indigent Population Christina Yek 1 ; Carolina De La Flor 1 ; Amit Singal 1 ; Mamta K. Jain 2 ;Ting-Yi Chen 1 ; Cindy L. Zoellner 1 ; Christian Mayorga 1 ; Lisa Casey 1 1 Univ of Texas Southwestern, Dallas, TX, USA; 2 Univ of Texas Southwestern Med Cntr, Dallas, TX, USA

Background: Direct-acting antivirals (DAAs) have revolutionized the management of chronic hepatitis C (HCV). However, high cost of drugs and limited clinic capacities remain significant barriers to treatment. The aim of our study was to examine the impact of coordinating minimal available resources to treat HCV-infected patients at a large urban safety-net hospital. Methods: Our cohort included all patients who started DAA-based HCV treatment between April 2014 and August 2015 at Parkland Memorial Hospital. Available clinic resources and staff included 0.4 FTE infectious disease/hepatology physician champions, 0.5 FTE nurse navigator, and 0.25 FTE mid-level provider that met once weekly for liver clinic. Results: During a 16-month period, 184 patients were started on DAAs, representing a 280% increase in the volume of HCV treatment initiation from historical rates at Parkland. Median age was 58 [IQR 54-61], 55%were male, and our cohort was racially diverse (43%White, 37% Black, 20% Hispanic, 1% Asian). 60% of patients had cirrhosis, 22%were treatment-experienced, 13% had HIV co-infection and 5%were liver transplant recipients. Nearly half (49%) of the patients had no insurance, 30% had Medicare, 20%Medicaid, and 1% commercial insurance; uninsured and Medicaid patients initiating treatment prior to January 2015 received medications through patient assistance programs. HCV regimens included 23% sofosbuvir (SOF) ±ribavirin (RBV), 38% simepravir (SMV) and SOF±RBV, 38% ledipasvir (LDV) and SOF±RBV, and 2% daclatasvir (DCV) and SOF. 56% of patients reported medication side effects including fatigue (35%), gastrointestinal upset (20%), rash (20%), mood disturbances (8%) and headache (6%). Treatment response was assessed in patients at 12 weeks after treatment completion (data available for 90 patients at time of submission). Sustained viral response (SVR12) was achieved in 76% (n=68), 7% (n=6) had viral relapse, 4% (n=4) stopped treatment due to serious adverse events and 13% (n=12) were lost to follow-up. Per protocol analysis, SVR12 was achieved in 87%. Conclusions: Our model of care increased treatment initiation and achieved exceptional effectiveness in a safety-net health system using only part-time staff. Loss to follow-up remained a problem in our indigent population and additional interventions may be needed to improve outcomes. Nevertheless, access to and effectiveness of HCV DAAs is high in our safety-net hospital, suggesting favorable outcomes can be achieved in limited resource settings. 588 Ledipasvir/Sofosbuvir Failures in the Real World: What Patients Are at Risk? Dost Sarpel 1 ; Alyson Harty 1 ; Donald Gardenier 1 ; Ponni Perumalswami 2 ; Michael P. Mullen 1 ; Ira M. Jacobson 3 ; Andrea Branch 1 ; Douglas Dieterich 2 1 Icahn Sch of Med at Mount Sinai, New York, NY, USA; 2 Mount Sinai Hosp, New York, NY, USA; 3 Mount Sinai Beth Israel, New York, NY, USA Background: Ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination resulted in sustained virologic response (SVR) rates of 93-97% for both treatment naïve and experienced genotype 1 HCV-infected patients with or without cirrhosis. As more patients are treated with this regimen, a population of treatment failures is emerging. We describe 13 patients who failed LDV/SOF despite having an undetectable viral load at the end of therapy. Methods: This observational cohort study was conducted on patients who failed LDV/SOF therapy at the Mount Sinai Medical Center during the interval between March and September 2015. Data were collected on age, sex, viral genotype, presence or absence of cirrhosis, prior history of hepatocellular carcinoma (HCC), co-infection with HIV, previous therapy regimen, and duration of LDV/SOF. Results: Thirteen patients failed treatment, and only one had HIV co-infection (Table). Ten (77%) were male with a mean age of 60 years (range 34-69). Most (n=11) had genotype 1 HCV, six had 1a, four had 1b, one had 1l. Eight (62%) had liver cirrhosis; among them, five had a history of hepatocellular carcinoma (HCC) that was treated by liver transplantation (n=2), by chemoembolization (n=2), or resection (n=1). Six of the 13 (46%) had a history of prior HCV treatment failure. All prior regimens were IFN/RBV based; one included telaprevir. Regarding LDV/SOF treatment, 11 (85%) had 12 weeks of therapy, one had 24 weeks, and one had eight weeks. Six relapsed by post treatment week (PTW) four, and all relapsed by PTW 13. NS3 and NS5A resistance panels have been sent on all patients and will be reported.

Poster Abstracts

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CROI 2016