CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

563 RESISTANCE-ASSOCIATED SUBSTITUTIONS (RAS) IN “UNUSUAL” HCV SUBTYPES Stephanie Popping 1 , Slim Fourati 2 , Anita Howe 3 , Velia C. Di Maio 4 , Adolfo D. Salazar 5 , C. Rodrigo 6 , Midori Kjellin 7 , Johan Lennerstrand 7 , Mark Douglas 8 , Francesca Ceccherini Silberstein 4 , P. Richard Harrigan 9 , Federico García 5 , Charles Boucher 1 , Jean-Michel Pawlotsky 2 1 Erasmus University Medical Center, Rotterdam, Netherlands, 2 Centre National de Réference des Hépatites B, C et delta, Créteil, France, 3 British Columbia Centre for Disease Control, BC, Canada, 4 University of Rome Tor Vergata, Rome, Italy, 5 Hospital Universitario San Cecilio, Granada, Spain, 6 University of New South Wales, Sydney, Australia, 7 Uppsala University, Uppsala, Sweden, 8 The University of Sydney, Syndey, Australia, 9 University of British Columbia, Vancouver, BC, Canada Background: “Unusual” Hepatitis C virus (HCV) subtypes in patients from Africa and Asia origin have been associated with a lower sustained virological response(SVR) to DAAs. This can be ascribed to polymorphisms at relevant amino acid positions compared to the most sensitive subtype in the same genotype. Using the global SHARED network, we aimed to assess the prevalence of RAS and RAS patterns at failure among unusual HCV subtypes, defined as GT1 non1a/b, GT2 non2a/b, GT3 non3a, GT-4 non4a/d, GT5, and GT6. Methods: We extracted data from the SHARED database of patients who did not achieve SVR. Only patients who failed DAA regimens recommended by EASL guidelines were included. Geno- and subtype were sequence-derived, and analyses grouped by subtype. RAS were analysed at positions according to the 2018 EASL guidelines. Results: We analysed 60 unusual subtypes among DAA failures, including: GT2c(n=8), GT3b(n=6), GT3h(n=7) and GT4r(n=10) followed by GT4v(n=3), GT2q,3k,4g,4o, and 6q(n=2, each), and GT1l,2j,3g,4b,4f,4k,4q,4t, 6h, 6p,6r and 6xe(n=1, each). Patients failed; SOF/DCV(n= 14), SOF/VEL +/- RBV(n=13), and EBR/GZR(n=10), SOF/LDV +/- RBV(n=10), G/P(n=5) or other regimens(n=2). At failure, all patients harbored NS5A RASs regardless of their subtype, with a mean number of 3 NS5A RAS per sample. Interestingly, failures with GT6h/p/r/ xe carried 5 to 6 NS5A polymorphisms possibly associated with reduced NS5A inhibitor susceptibility. All GT3h failures harbored a S62M RAS with unknown impact, 71% of which were combined with the Y93H/F. All GT4r failures harbored L28M/T/V RAS in association with L30R with or without L31M/F. All GT-3b and GT3g harbored the A30K+L31M+S62D/E/I combination. Additionally, among NS3 failures RAS at position 168(D168V/N/E) were observed in 50% of patients(n=6/12). Importantly, combinations of several NS3 RAS were detected in specific subtypes(GT4g with R155Q+A156T/I/V+D168N, GT6q with A156F+D168V in patients failing GZP/ELB and G/P respectively). The S282T variant in NS5B occurred in 20% of GT4r patients(n=1). Conclusion: Unusual subtypes(mainly but not only GT3b, 3h, and 4r) may be overrepresented among failures, suggesting lower SVR rates due to the presence of polymorphisms. In-depth characterization of these subtypes is crucial, in Africa and Asia where these subtypes are common as well as in countries of immigration from these regions. Our results emphasize the need for identification of RAS in these subtypes and their in vitro drug susceptibilities. 564 TRANSMISSION OF THE NS5A-RESISTANT VARIANT M28V AMONG ACUTE HIV/HCV COINFECTED MSM Stephanie Popping 1 , Rosanne Verwijs 1 , Lize Cuypers 2 , Mark Claassen 3 , Guido Van Den Berk 4 , Anja De Weggheleire 5 , Joop E. Arends 6 , Anne Boerekamps 1 , Richard Molenkamp 1 , Marion Koopmans 1 , Annelies Verbon 1 , Charles Boucher 1 , Bart Rijnders 1 , David Van De Vijver 1 1 Erasmus University Medical Center, Rotterdam, Netherlands, 2 Katholieke University Leuven, Leuven, Belgium, 3 Rijnstate Hospital, Arnhem, Netherlands, 4 OLVG, Amsterdam, Netherlands, 5 Institute of Tropical Medicine, Antwerp, Belgium, 6 University Medical Center Utrecht, Utrecht, Netherlands Background: The World Health Organization (WHO) has declared to eliminate hepatitis C virus (HCV) as a global health threat by 2030. To achieve this goal, WHO recommends expanding direct-acting antivirals (DAAs), which can achieve high cure rates and thereby prevent onward transmission. Widespread use of DAAs has drastically reduced new HCV infections in the Netherlands. Unfortunately, virological failure can still occur and is associated with emergence of resistance associated substitutions (RAS). Transmission of RAS can hamper HCV elimination efforts. In Western Europe, HCV is predominantly transmitted between HIV-positive men-who-have-sex-with-men (MSM). We investigated the transmission dynamics of HCV and its specific RAS among MSM, before and after the widespread use of DAAs.

1 Seconda Università degli Studi di Napoli, Napoli, Italy, 2 Azienda Ospedaliera Sant'Anna e San Sebastiano di Caserta, Caserta, Italy, 3 Evangelical Hospital Villa Betania Naples, Naples, Italy, 4 AORN dei Colli, Naples, Italy, 5 University of Naples Federico II, Naples, Italy Background: Despite the excellent efficacy, direct-acting antivirals (DAA)- regimens are associated with failure in about 5% of cases. To characterize the virological patterns and the resistant-associated substitutions (RASs) in the patients with failure to second-line DAA-regimen. It may help to identify the best approach of new line DAA-regimen. Methods: All the consecutive 63 HCV patients (pts) with failure to IFN-free regimen observed at the laboratory of infectious diseases of University of Campania, Naples from January 2018 to February 2019 were were enrolled. All the pts had been treated with DAA-regimens according HCV genotype, international guidelines and local availability. Sanger sequencing of NS3 (for genotypes 1 and 4), NS5A and NS5B (for all genotypes) was performed at failure by home-made protocols. Results: Table 1 shows characteristics of patients enrolled and type of treatment. According to therapeutic outcome, 90.5% relapse, 4.7% breakthrough and 4.7% non-response. Among the 63 patients failed at three therapeutic regimens, 19 (30.1%) were been treated with Sofosbuvir+Velpatasvir, 11 (17.4%) with Glecaprevir/Pibrentasvir and 33 (52.4%) with Elbasvir/Grazoprevir. The duration of DAA in months, median (range) 12 (8-24), the timing of resistence test in months at the end of treatment, median (range) 5 (1-19). The NS5A-RASs were more frequent in Sofosbuvir+Velpatasvir (17/19, 89.5%) and in Grazoprevir/Elbasvir (32/33, 97%) failed patients than in Glecaprevir/Pibrentasvir (4/11, 36.7%) failed patients (p=0,002 and 0,000 respectively). According to Sofosbuvir/Velpatasvir regimen 36.4% pts showed at least 2 RASs in at least two HCV region including NS5A and 70.3% pts showed at least 2 RASs only in NS5A region. Considering Grazoprevir/ Elbasvir regimen 27.3% pts showed at least 2 RASs in at least two HCV region including NS5A and 88% pts showed at least 2 RASs only in NS5A region. (p=0.00). All 21 re-treated patients with Sofosbuvir/Velpatasvir /Voxilaprevir, obtained with SVR. The re-treatment was guided by genotyping test. Conclusion: Patients with failure to a second-line therapeutic regimens frequently present mutations above all in the NS5A region. At re-treatment all patients obtained SVR. According to our real-life experience, re-treatment with the new regimes is effective and safe.

Poster Abstracts

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