CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: We included 90 plasma samples from 101 acute HCV genotype 1a infected HIV-positive MSM that were diagnosed in one Belgian and ten Dutch HIV-treatment centres between 2013 and 2018. Samples were subjected to Sanger sequencing or Illumina sequencing, using a 15% cut-off for variant calling. RAS were defined based on the EASL guidelines. Phylogenetic analysis was based on concatenated NS5A and NS5B sequences from the included plasma samples and from 425 publicly available sequences. Clusters were defined based on a bootstrap support of 100% and a genetic distance of <1.5% (maximum likelihood analysis GTR+G4+I). Results: We found strong clustering of HCV sequences and distinguished five major clusters including 84% of individuals. Four clusters included at least 10 individuals that were sampled in different treatment centres. One-third of all new HCV infections (28 individuals) clustered in one large cluster, of which 96% harboured the NS5A RAS M28V. The number of clusters and the proportion of individuals belonging to a cluster remained stable in the period before and after introduction of DAAs in 2015. Conclusion: Large clusters of acute HCV infections were detected in the years preceding as well as after introduction of DAAs, suggesting active transmission of HCV among HIV-infected MSM. A stable transmission of the RAS M28V was found, which is known to influence susceptibility to some of the NS5A inhibitors. The continuing transmission of M28V illustrates the need for resistance surveillance in populations with ongoing HCV transmission. Despite elimination efforts, most clusters persisted, highlighting the need for targeted monitoring and risk reduction strategies to achieve HCV elimination. 565 RESISTANCE ANALYSIS IN HCV-3–INFECTED PATIENTS WITHIN THE ITALIAN NETWORK VIRONET-C Velia Chiara Di Maio 1 , Silvia Barbaliscia 1 , Elisabetta Teti 2 , Caterina Pasquazzi 3 , Stefania Paolucci 4 , Teresa Pollicino 5 , Bianca Bruzzone 6 , Nicola Coppola 7 , Valeria Micheli 8 , Fausto Baldanti 9 , Giustino Parruti 10 , Mario Angelico 2 , Massimo Andreoni 2 , Carlo Federico Perno 11 , Francesca Ceccherini Silberstein 1 1 University of Rome Tor Vergata, Rome, Italy, 2 Hospital of Rome Tor Vergata, Rome, Italy, 3 Sapienza University of Rome, Rome, Italy, 4 IRCCS Policlinico San Matteo Foundation, Pavia, Italy, 5 University Hospital of Messina, Messina, Italy, 6 IRCCS AOU San Martino-IST, Genoa, Italy, 7 University of Campania Luigi Vanvitelli, Naples, Italy, 8 Luigi Sacco University Hospital, Milan, Italy, 9 IRCCS Policlinic Foundation San Matteo, Pavia, Italy, 10 Pescara Hospital, Pescara, Italy, 11 University of Milan, Milan, Italy Background: This study aimed to investigate the presence and role of resistance-associated-substitutions (RASs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3 infected patients (pts, 417 DAA-naïve and 135 DAA-failures, of them,13 at both baseline [BL] and failure), were analysed. Sanger-sequencing of NS3/NS5A/NS5B was performed by home-made protocols. Results: The majority of pts were male (79%) and cirrhotic (50%). 23 pts (14%) were HIV-coinfected. Phylogenetic analysis classified sequences as GT3a-3b- 3g-3h (98%-0.4%-0.2%-1.2%), respectively. Notably, 39 pts were previously misclassified as infected with GT indeterminate, non-3, or mixed (N=10/22/7, respectively). Overall, 135 GT3 pts failed an interferon-free regimen: sofosbuvir(SOF)/daclatasvir(DCV) or velpatasvir(VEL)±RBV (N=91/15) and glecaprevir(G)/pibrentasvir(P) (N=9). Moreover, 14.8% of pts were treated with suboptimal regimens for GT3: 3D±RBV (Paritaprevir/r+Ombitasvir+Dasabuvir, N=15), SOF+Simeprevir (N=1) or SOF/ Ledipasvir (LDV)+RBV (N=4). In DAA- naïve pts, overall RAS prevalence was 16% (NS5A-RAS:15.5%). At failure, 81.5% pts showed at least one RAS related to the DAA-regimen, of whom 11/25 (44%) in NS3, 109/135 (81%) in NS5A, 7/111 (6%) in NS5B SOF-failures. In NS5A-failures, Y93H was the most prevalent RAS (68.5% vs 5% DAA-naïve, p<0.001) followed by A30K (13% vs 3% in DAA-naïve, p<0.001). Interestingly, analysing the BL samples, a higher prevalence of NS5A-RASs was observed before treatment in DAA-failures (5/13, 38%) vs DAA-naïve pts (61/393, 15.5%, p=0.04). The single Y93H was detected mainly after SOF/DCV or VEL (67% and 60%) and 3D (80%) failures. By contrast, NS5A-RASs patterns (mostly A30K+Y93H) were frequently observed (55%) after G/P failure. In NS5B, RASs L159F and S282T were detected only in SOF/DCV failures (5% and 1%, respectively). Regarding DAA-naïve pts with an available outcome, 228 were treated with the following regimens: SOF/ DCV or VEL±RBV (N=150/47) and G/P (N=31). Overall, 94% achieved a SVR. In particular, for pts with BL Y93H and/or A30K the overall SVR rate was 72% vs 96% for pts without NS5A RASs (p=0.002).

Conclusion: In this large cohort of GT3 infected pts, the majority of failures harbored resistant HCV variants carrying one or two NS5A RASs, the most frequent being Y93H. The presence of natural NS5A RAS before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens. 566 BARRIERS TO DIRECTLY ACTING ANTIVIRALS THERAPY AMONG HIV/HCV- COINFECTED ADULTS Gina M. Simoncini 1 , Qingjiang Hou 2 , Kate Buchacz 3 , Ellen Tedaldi 1 , Frank J. Palella 4 , Jack Fuhrer 5 , Richard M. Novak 6 , Cynthia Mayer 7 , David E. Koren 1 , Linda A. Battalora 8 , Stockton Mayer 9 , Stacey Purinton 2 , Jun Li 3 , for the HIV Outpatient Study (HOPS) Investigators 1 Temple University, Philadelphia, PA, USA, 2 Cerner Corp, Kansas City, MO, USA, 3 CDC, Atlanta, GA, USA, 4 Northwestern University, Evanston, IL, USA, 5 Stony Brook University, Stony Brook, NY, USA, 6 University of Illinois at Chicago, Chicago, IL, USA, 7 St. Joseph's Comprehensive Research Institute, Tampa, FL, USA, 8 Colorado School of Mines, Golden, CO, USA, 9 University of Illinois College of Medicine, Peoria, IL, USA Background: HIV and chronic hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality; yet many people co-infected with HIV/HCV remain untreated for HCV infection. We explored demographic, clinical variables and social determinants of health among coinfected participants in routine HIV care that may differentiate those treated versus untreated with directly-acting antivirals (DAAs). Methods: We analyzed medical record data as of December 31, 2018 of HIV Outpatient Study (HOPS) participants seen at 9 U.S. clinics who were diagnosed with HCV with at least one confirmatory HCV RNA viral load (VL) test or genotype test since June 30, 2010. DAA therapy was determined by medication prescription from the HOPS database. Participants treated with interferon/ ribavirin along with DAA were excluded. Based on bivariate analyses, factors associated with the probability of receiving DAA therapy were further evaluated by multivariable logistic regression. Results: Among 306 eligible participants, median age was 52 years, median duration of follow up was 3.96 years, 97 (32%) were female, and 202 (66%) were non-white, 131 (42.8%) were prescribed DAA therapy, 127 (96.9%) had at least one follow-up HCV VL and 13 (9.9%) participants remained HCV viremic 12 months after initiating DAA therapy, resulting in an overall cure rate of 90.1%. DAA treatment was not associated with patient’s race and ethnicity (p=0.17), history of substance abuse (p=0.53), nor a mental health condition (p=0.43). Multivariable logistic regression analyses indicated that participants who were older (p=0.03), with health insurance (p=0.01), higher CD4 range (p<0.001), and injection drug use as the HIV risk category (p=0.03), were more likely to receive DAA therapy (Figure). Compared with the publicly insured, privately insured participants were more likely to receive DAA with an odds ratio of 2.30 (95% confidence interval: 1.32-4.12). Conclusion: Only 42.8% of HIV/HCV-coinfected participants have been treated in the HOPS cohort. Factors associated with lower uptake of DAA therapy included younger age, sexual transmission as the HIV risk factor, lower CD4 range, and public or no insurance. Substance use, mental health diagnosis, race, and ethnicity were not associated with DAA treatment. Improved insurance coverage and expanded clinical care access to younger, presumably healthier individuals, is needed to bridge the treatment gap.

Poster Abstracts

CROI 2020 203