Prevalence of baseline resistance-associated substitutions to NS5A and NS5B in patients infected with hepatitis c virus genotype 1 in Argentina

RIDRUEJO E; PEREZ PS; FLICHMAN D; GARCÍA GH; NEUKAM K; MARTINEZ AP; ROMANO V; DI LELLO F

Punta Cana

Congreso; Congreso de la Asociación Latinoamericana para el Estudio del Hígado; 2018

Asociación Latinoamericana para el Estudio del Hígado

ABSTRACTIntroduction: The incorporation of direct acting antivirals (DAA) in the treatment of HCV significantly increases the sustained virologic response rates. However, despite the greater potency offered by these antivirals, drug resistance plays a key role in patients with failure to DAA. Nevertheless, there is scarce information about the prevalence of Resistance-Associated Substitutions (RAS) in Argentina.Objective: The aim of this study was to analyze HCV variants resistant to NS5A and NS5B inhibitors in naïve patients infected with HCV genotype 1 from the Hepatology Unit of a tertiary care center in Buenos Aires, Argentina. Methods: In this retrospective cross-sectional study, 79 patients infected with HCV-1 were analyzed for NS5A and 72 for NS5B. In particular, 16 positions related with resistance to treatment were analyzed in this work: M28, Q30, L31, P32, H58, A92 and Y93 for NS5A and S96, N142, L159, E237, S282, C289, C316, L320 and V321 for NS5B.Results: Amino acid substitutions conferring resistance to NS5A inhibitors were detected as follow: L31M 5 (6.32%), H58L 1 (1.26%), H58R 1 (1.26%), T64S 2 (2.52%), A92T 1 (1.26%), A92V 1 (1.26%) and Y93H 2 (2.52%). For NS5B, None of the 26 patient infected with HCV-1a had RAS in NS5B. On the other hand, 2/46 (4.3%) infected with HCV-1b had RAS. One patient present a RAS in L159F and one patient present a double RAS (L159F and C316N). Conclusion: As it was reported in previous studies, RAS were more frequent in NS5A than in NS5B (16.4% vs. 2.7%; p: 0.005). However, the prevalence of each RAS in NS5A varies markedly depending on the geographic region analyzed. In this sense, the present work supports the need for more studies of molecular epidemiology of RAS in order to improve the local treatment guides with the incorporation of autochthonous data.