RESUMO
Background: The development of direct-acting antiviral agents [DAAs] has revolutionized the treatment of HCV infection. The main challenge to HCV effective treatment with daas is the emergence of HCV drug-resistant variants. Detection of resistance associated variants is of importance in clinical settings in order to optimize DAA regimens, maximize success rates and reduce the impact of treatment failure
Objectives: The prevalence of possible mutations expected to induce potential directly acting antiviral agent [DAA] resistance was investigated in twenty DAAs naïve HCV infected patients
Methodology: The twenty HCV isolates were genotyped using the full length NS3/4A, NS5B, and two third of the carboxy terminal region [including ISDR] of NS5A gene sequences
Results: Eighteen [90%] out of 20 strains were diagnosed as subgenotype 4a while 2 [10%] were of subgenotype 4n, Amino acid frequencies at each position in the NS3 protease sequence were determined with the VESPA software program. Twenty four Genotype4-specific amino acid signatures were present in almost all of our sequences, but were absent from all other genotypes. Among the twenty four amino acid signatures only one mutation at position 41 [T/S] reported to be associated with resistance to protease inhibitors. Compared to the wild type HCV GT-4; nine mutations were detected among our isolates at a frequency ranging from 27% to 100%. None of these mutations were associated with resistance to protease inhibitors. Forty three mutations were detected among our isolates at a much lower frequency ranging from 5.5% to 16.6%. Only 5 out of them were associated with protease inhibitor resistance. Amplification of domain II and III including the interferon sensitivity-determining region and the interferon/ribavirin resistance-determining region of the NS5a region showed a number of mutations exceeding 4 in all isolates and 82.3% of them had from 10-30 mutations. Thirty two Genotype 4-specific amino acid signatures were present in almost all of our sequences and absent from all other genotypes. The primary NS5B nucleoside polymerase inhibitors [NPIs] resistance variant 282T was not detected in our isolates
Conclusion: The large number of natural polymorphism of HCV 4 isolates as well as the large number of mutations detected in this study and different from those associated with DAA resistance makes it more practical to detect resistance associated mutations in DAA treatment failure then to look for these mutations in naïve patients