Natural prevalence of hepatitis C virus (HCV) variants resistant to protease and polymerase inhibitors in patients infected with HCV genotype 1 in Tunisia.
Hepatitis C virus (HCV) protease inhibitors (PIs) and polymerase inhibitors: nucleos(t)ide inhibitors (NS5B-NIs) and non-nucleos(t)ide inhibitors (NS5B-NNIs) have been recently developed to inhibit protease (NS3) or polymerase (NS5B) activities. The drawback of antiviral treatment is the emergence of resistance mutations to the drugs. The prevalence of such mutations conferring resistance to PIs, NS5B-NIs, and NS5B-NNIs before treatment has not been investigated so far in the Tunisian population. The aim of this study was to investigate the prevalence of known substitutions conferring resistance to HCV-PIs, NS5B-NIs, and NS5B-NNIs in 149 untreated patients naïve of any novel or investigational anti-HCV drugs and infected with HCV genotype 1 (genotype 1a = 7; genotype 1b = 142). Twelve sequences (9.2%) of the 131/149 HCV NS3 sequences analyzed showed amino-acid substitutions associated with HCV PIs resistance mutations (T54S, n = 4 (3%); V55A, n = 2 (1.5%); Q80K, n = 4 (3%); R155K, n = 1 (0.7%); A156V, n = 1 (0.7%)). One (1%) of the 95/149 HCV NS5B sequences analyzed showed the substitution V321I conferring resistance to NS5B-NIs, while 34 of 95 (35.8%) showed substitutions conferring resistance to NS5B-NNIs (C316N, n = 2 (2%); M414L, n = 1 (1%); A421V, n = 8 (8.5%); M423A, n = 1 (1%); M423T, n = 2 (2%); I424V, n = 5 (5.2%); C445F, n = 1 (1%); I482T, n = 2 (2%); V494A, n = 1 (1%); P496A, n = 1 (1%); V499A, n = 15 (16%); S556G, n = 5 (5.2%)). Naturally occurring substitutions conferring resistance to NS3 or NS5B inhibitors exist in a substantial proportion of Tunisian treatment-naïve patients infected with HCV genotype 1. Their influence on treatment outcome should be assessed.
LR11-IPT-09, Epidémiologie et diversité génétique des virus hépatiques et entériques humain, Institut Pasteur de Tunis, Tunis, Tunisia; CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France; Virology Laboratory, Bordeaux University Hospital, Bordeaux, France.
Jameleddine
J
Aissa Larousse
Pascale
P
Trimoulet
Patricia
P
Recordon-Pinson
Jennnifer
J
Papuchon
Mohamed Mssadak
MM
Azzouz
Nabyl
N
Ben Mami
Imed
I
Cheikh
Henda
H
Triki
Hervé
H
Fleury
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015995:Prevalence; D014416:Tunisia / Q000453:epidemiology; D055815:Young Adult
NS5B-NNIs); polymerase inhibitors (NS5B-NIs; protease inhibitors (PIs); resistance mutations