Use of next-generation sequencing in the CHAT study (acute HCV in HIV): effect of baseline resistance-associated NS3 variants on treatment failure

HIV Clinical Trials
Gurmit Kaur Jagjit SinghMark Nelson

Abstract

Background The epidemic of acute HCV infection among HIV-infected men who have sex with men (MSM) is ongoing. Transmission of drug-resistant variants (DRVs) after HCV treatment failure could pose a major threat to the effectiveness of future therapies. We determined the baseline prevalence of pre-existing DRVs in the HCV NS3 protease gene and their effects on the addition of telaprevir (TVR) to standard pegylated interferon and ribavirin (PEG-IFN/RBV) for acute HCV infection in individuals enrolled in a multicentre randomized controlled trial (2013 and 2014). Methods The HCV NS3 viral protease was analyzed using Sanger and next-generation sequencing (NGS) for DRVs at baseline (n = 31), and at viral breakthrough following TVR-based treatment (n = 3) or PEG-IFN/RBV alone (n = 2). Results Sequence analysis indicated that all individuals were infected with HCV genotype 1a. Complete (100%) concordance was seen between Sanger and NGS for high levels of mutant viral populations. The simeprevir-associated Q80K variant was present at high frequency in the German samples (7/11-64%) and infrequently in the UK samples (1/20-5%). In the three TVR-based treatment failures, V36M/l and R155K/T emerged, but not R155G which was detectable at low...Continue Reading

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Citations

Jul 19, 2019·Critical Reviews in Clinical Laboratory Sciences·Lize CuypersMahmoud Reza Pourkarim
Oct 16, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Gül R YilmazJürgen K Rockstroh

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