CROI 2020 Abstract eBook

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Poster Abstracts

559 CAUSE OF DEATH AMONG THOSE DIAGNOSED WITH HEPATITIS C IN WASHINGTON, DC, 2009-2017 Jenevieve Opoku 1 , Adam Allston 1 1 District of Columbia Department of Health, Washington, DC, USA Background: There has been very limited research on mortality among people diagnosed with Hepatitis C (HCV) in the District of Columbia (DC). As the opioid use crisis continues to grow both nationally and locally, knowledge of how opiate use deaths has had an impact on residents, especially among those with HCV, may be useful in strategizing intervention programs. The purpose of this analysis is to describe the differentiating causes of death among those diagnosed with HCV in DC. Methods: Data from DC Health HCV surveillance system and Vital Statistics records were matched to identify DC residents diagnosed with HCV who died between 2009 and 2017. Bivariate analysis was performed to identify differences between opiate overdose and non-opiate overdose deaths by demographics including gender identity, race/ethnicity age at death, HIV co- infection, year of death, HCV diagnosis class and last RNA results. Standardized mortality ratios for all causes of death were calculated and adjusted for age, sex, and death year. Results: Between 2009 and 2017, there were 4,633 deaths among DC residents diagnosed with HCV. Majority of deaths were among those who were male (68.1%), Black (60.2%) and died between the ages of 50 and 69 (76.5%). Cardiovascular disease was the leading primary cause of death (30.6%) followed by non-AIDS defining cancers (12.6%), opiate overdose (9.8%) and liver diseases (8.9%). Over the 9-year period, there was a 561% increase in opiate overdose deaths compared to a 69.1% decrease in liver-related deaths. Compared to persons who had a non-opiate related death between 2009 and 2017, HCV cases with a death due to opiate overdose were more likely to have a death age between the ages of 50-69 (84.1% vs 75.6%, p<.0001), have a year of death in 2017 (26.2% vs 13.6%, p<.0001), and have a positive/detectable result at their last RNA screening (62.1% vs 53.7%, p<.0001). There were no differences by gender identity, race/ethnicity and HIV-coinfection. Risk of dying from opiate- overdose was significantly greater than liver-related causes (p=0.0009), with the greatest excess risk in men aged 50-69 years (12.58, 5.91-26.78). Conclusion: This analysis highlights that older adult males with hepatitis C face a higher mortality risk from continued opiate drug use than from their hepatitis infection. As local governments continue to strategize interventions around opioid overdose, it will be important to include approaches around specific subpopulations affected by HCV. 560 CAUSES OF DEATH IN PERSONS WITH AND WITHOUT HCV INFECTION Adeel A. Butt 1 , for the ERCHIVES Study Team 1 Weill Cornell Medicine, New York, NY, USA Background: HCV is associated with a higher risk of overall mortality and several hepatic and extrahepatic consequences, including atherosclerotic cardiovascular disease (ACVD), diabetes, chronic kidney disease, hepatocellular carcinoma (HCC) and certain non-liver cancers. Whether the excess mortality is primarily due to liver-related or other causes is unknown. Knowing the most common causes of death is critically important to design targeted strategies to reduce mortality in persons with HCV infection. Our objective was to determine the most common causes of death in persons with and without HCV infection. Methods: HCV infected and uninfected participants in the ERCHIVS cohort between Jan 1, 2002 to December 31, 2016 were included. To determine cause of death, we linked deceased ERCHIVES participants to the National Death Index (NDI) data updated to end of 2016. NDI is a part of the National Center for Health Statistics and compiles cause of death data from the death certificates obtained from state vital statistics offices. Cause of death was retrieved from the underlying cause listed on the death certificate by using ICD‐10 codes. Each cause of death was categorized according to the primary organ system listed in the cause of death form. Liver-related causes included viral hepatitis and HCC, but excluded alcohol-related liver disease. Malignancy included all malignant cancers but excluded benign neoplasms and HCC. Self-harm category included suicide, intentional self-harm, intentional and unintentional drug-overdose but excluded accidental death due to external causes, e.g. road traffic accidents, homicide and falls. Results: Among 754,670 ERCHIVES participants, a total of 182,744 deaths were recorded during the study period (113,650 in HCV+ and 69,094 in HCV-). Among persons with HCV, the five most common causes of death were: Liver related (19.6%); malignancy (18.0%); ASCVD (16.8%); self-harm (6.2%); pulmonary

disease (5.6%). Among those without HCV, the five most common causes were: Malignancy (25.2%); ASCVD (23.0%); pulmonary disease (7.8%); infections (5.4%); endocrine including diabetes (5.1%). Conclusion: Liver disease, ASCVD and malignancy are responsible for the majority of deaths HCV+ persons. Self-harm is responsible for twice as many deaths in HCV+ vs. HCV-. Targeted strategies to reduce non-liver-related causes of death are needed to reduce mortality further in HCV+ persons.

561 RESOLVING HCV SUBTYPES IN A BELGIAN COHORT BY FULL GENOME NEXT-GENERATION SEQUENCING Kasper T. Christensen 1 , Florian Pierard 1 , Kurt Beuselinck 2 , David Bonsall 3 , Rory Bowden 3 , Katrien Lagrou 1 , Frederik Nevens 1 , Peter Simmonds 3 , Anne-Mieke Vandamme 1 , Eric Van Wijngaerden 1 , Lize Cuypers 1 , Kristel Van Laethem 1 1 Katholieke University Leuven, Leuven, Belgium, 2 University Hospitals Leuven, Leuven, Belgium, 3 University of Oxford, Oxford, UK Background: In order to reach WHOs goal of HCV elimination it has been suggested to prioritize populations that are actively propagating infection, given e.g. several outbreaks of HCV among HIV-infected men who have sex with men in the last decade. Genotyping the infecting virus is part of routine care to guide antiviral treatment, but commercial assays have been shown to occasionally report inaccurate results. In this study, we use next-generation sequencing (NGS) to increase the discriminatory power and evaluate the accuracy of genotyping in routine HCV care. Methods: From the University Hospitals of Leuven, Belgium, 64 samples from patients with HIV/HCV co-infection were selected and matched with 86 samples from HCV mono-infected patients to exhibit a similar genotype distribution based on determinations with the VERSANT HCV Genotype Assay. For the co-infected patients, 30.4%, 66.1%, and 46.4% reported intravenous drug use, same-sex practices, and being born outside of Belgium, respectively. HCV genomes were generated using the veSeq-HCV protocol and an in-house optimized bioinformatics pipeline. Concordance between geno- and subtypes designated by VERSANT and the Hepatitis C Virus Phylogenetic Typing Tool v2.4 using the generated consensus sequence was determined. Results: When considering only the 87 samples with an associated VERSANT genotyping record and >90% of the coding region of HCV sequenced to a depth >100, the genotype distribution following NGS was: genotype 1: 72% (42: 1b, 21: 1a), genotype 4: 15% (8: 4d, 2: 4k, 1 each: 4q, 4c, 4r), genotype 3: 9% (3: 3a) and genotype 2: 3% (1 each: 2a, 2c, 2i). Despite not all samples passing quality control thresholds, 112 samples had both a genotype determined by VERSANT and the phylogenetic typing tool. Of these, 78% had identical subtypes using VERSANT and NGS, 20% had a genotype specified into one of its constituent subtypes, one sample had a different subtype (VERSANT: 1b, NGS: 1a) and one had a different genotype (VERSANT: 1a, NGS: 4d). Based on near full-genome coverage by contigs of different genotypes generated de novo, 5 samples showed signs of mixed infection not indicated by VERSANT. Conclusion: While the applied sequencing strategy requires further optimisation to reliably classify all geno- and subtypes across a broad viral load range, a good overall concordance was found with the genotype determined by VERSANT. The higher resolution of NGS proves capable of resolving specific subtypes and detecting cases of potential mixed infections. 562 VIROLOGIC PATTERNS OF HCV PATIENTS WITH FAILURE TO SECOND- GENERATION DAAs Mario Starace 1 , Mariantonietta Pisaturo 1 , Carmine Minichini 1 , Stefania De Pascalis 1 , Margherita Macera 1 , Laura Occhiello 1 , Alessandra Di Fraia 1 , Loredana Alessio 2 , Vincenzo Messina 2 , Ernesto Claar 3 , Tiziana Ascione 4 , Aldo Marrone 1 , Ivan Gentile 5 , Giovanni Battista Gaeta 1 , Nicola Coppola 1

Poster Abstracts

CROI 2020 201