CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

560 HIGH RATES OF HCV CURE AMONG URBAN BLACK AND NON-BLACK HIV-INFECTED PATIENTS Oluwaseun Falade-Nwulia 1 , Juhi Moon 1 , Geetanjali Chander 1 , Tanyaporn Wansom 2 , Catherine Sutcliffe 1 , Shruti H. Mehta 1 , David Thomas 1 , Richard D. Moore 1 , Mark Sulkowski 1 1 Johsn Hopkins Univ, Baltimore, MD, USA, 4 US Military HIV Rsr Prog, Bethesda, MD, USA Background: Generally, HCV cure rates have been similar in patients with and without HIV coinfection; however, in the ION-4 study, black patients treated with sofosbuvir/ ledipasvir (SOF/LDV) were significantly less likely to achieve cure (90%) compared to non-black patients (99%). There are limited real world data on the effectiveness of oral direct acting antivirals (DAAs) in predominantly minority HIV/HCV coinfected populations. Methods: We analyzed HCV treatment outcomes among 255 HCV coinfected patients initiating DAAs between February 2014 and March 2016; all were enrolled in an ongoing prospective HIV cohort in Baltimore, MD. To facilitate adherence, patients received standardized HIV nurse/pharmacy support which included nurse visits and telephone calls. Demographics, laboratory test results and DAAs prescribed were extracted from the electronic medical record. Results: The median age was 43 years, 87%were black, 73%male, 69% had a history of injection drug use (IDU), 45% a history of hazardous alcohol use and 57% a comorbid psychiatric diagnosis. Median CD4 count was 577 (IQR 397-820) cells/mm3; most (97%) were on antiretrovirals and had HIV RNA <200 copies/ml (95%) and were infected with HCV genotype 1 (98%). Over 60% had significant fibrosis (FIB4 score 1.45-3.25 (44%) and >3.25 (17%, cirrhosis) and 30%were HCV treatment experienced. The majority of patients received SOF/LDV with or without ribavirin (91%) and were treated for 12 weeks (80%) whereas 4% and 15% received treatment for 8 weeks or less and 24 weeks, respectively. Overall, the cure rate was 96% (95% confidence interval [CI] 93-98) and did not vary by race (Black, 96% [95% CI 93-98]; Non-black 97%, [95% CI 83-99]) , HCV treatment experience (Naïve, 96% [95% CI 92-98]; Experienced, 97% [95% CI 91-100], history of IDU, alcohol use or psychiatric diagnosis history. Nine patients did not achieve cure; all were prescribed SOF/LDV without ribavirin for 12 weeks. Of these, 4 discontinued treatment prematurely (< 4 weeks), 3 had decompensated cirrhosis or were treatment-experienced and 2 had genotype 1b infection and did not report missed doses. Treatment was well-tolerated; only 1 patient discontinued due to side effects. Conclusion: HCV treatment was highly effective among HIV-infected patients who received care using a standard nurse/pharmacist adherence support program. Our results from an urban clinical practice suggest that race and psychosocial comorbidity may not be barriers to HCV elimination 561 GLOBAL ORIGINS OF RESISTANCE-ASSOCIATED VARIANTS IN THE NS5A REGION OF HCV Bradley R. Jones 1 , Jeffrey Joy 2 1 BC Cntr for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada, 2 Univ of British Columbia, Vancouver, British Columbia, Canada Background: Hepatitis C virus (HCV) contains a variety of naturally occurring polymorphisms in the nonstructural protein 5A (NS5A) that reduce susceptibility to currently approved NS5A inhibitors. Previous investigations showed the Q80K mutation in the NS3 region of HCV has a common origin in the world population around 1930 in genotype 1a strongly coupled to substitutions A915/T, S147N or V29A. We sought to reconstruct the evolutionary history of the NS5A resistance-associated substitutions (RASs). Methods: We collected more than 200,000 HCV sequences from global databases. Sequences were aligned using MAFFT v.7.54b and visually inspected using AliView v.1.18. After discarding sequences from the same patient and sequences that do not cover NS5A by 75%, we were left with 1,613 sequences. RASs were defined as substitutions in the NS5A gene previously identified based on literature sources. We inferred a phylogenetic tree for genotype specific datasets (1a, 1b, and 3a) under approximate maximum likelihood as implemented in FastTree2. Resulting phylogenies were rescaled to units of time using the R package ape. Next, we reconstructed the ancestral sequences at the nodes of the trees using MG94xREV codon model. Finally, NS5A RASs were mapped onto the resulting trees to recover patterns of ancestry. Results: We found, in contrast to Q80K in NS3, that most NS5A RAVs do not have a common origin, but rather each has evolved independently many times. They are widely dispersed amongst the phylogenetic trees of each genotype. Of the 22 types of RASs found in the total population, only 6 had origins that were not at the tips of the tree, each which had less than 5 RAS descendants. All of these RASs had their origins at tips of the tree, indicating recent origins. While the Q80K polymorphism has a highly localized origin in North America, we find that NS5A RASs have no strong pattern with respect to geography, with the overall prevalence ranging from 0.06% to 5%. Conclusion: The inferred distribution of RASs in the NS5A region and frequency of their origin suggest that, unlike Q80K, there is a low fitness barrier without the need for co- evolution of compensatory mutations. A low fitness barrier may allow rapid selection of de novo resistance to NS5A inhibitors during therapy. 562 IMPACT OF HCV NS5A RESISTANCE ON TREATMENT RESPONSE IN HIV AND HIV/HCV PATIENTS Itziar Carrasco Garcia 1 , Ana Arias 2 , Laura Benitez 2 , Silvia Requena 1 , Miriam Cuesta 1 , Luis Otero 3 , Valentin Cuervas-Mons 2 , Carmen de Mendoza Fernández 2 , for the Internal Medicine Department

Poster and Themed Discussion Abstracts

CROI 2017 236