Drug Resistance Against HCV in Direct-Acting Antiviral Treatments.

VIRAL HEPATIT DERGISI-VIRAL HEPATITIS JOURNAL, cilt.29, sa.3, ss.90-94, 2023 (ESCI)

Approved treatment protocols for hepatitis C virus (HCV) include

direct-acting antiviral drugs (DAA), which consist of NS3 protease

inhibitors (PI), NS5A replication complex inhibitors, and NS5B

polymerase nucleoside and non-nucleoside inhibitors (NNI). First-

generation DAAs are effective in specific genotypes (GT), such

as NS5AIs (dasabuvir), PIs (asunaprevir, grazoprevir, paritaprevir/r,

and simeprevir), and NNIs (ledipasvir, ombitasvir, and elbasvir).

Second-generation DAAs are “pan-genotypic” and include NS5AIs

(velpatasvir and pibrentasvir), PIs (voxilaprevir and glecaprevir),

and an NSBNI (sofosbuvir). DAAs can potentially cure people with

hepatitis C. However, although generally well tolerated, DAAs have

not been observed to produce sustained virological response in

some patients. Resistance-associated amino acid changes (RAS),

which can lead to treatment failure, may be the reason for this. The

RASs can occur naturally or during treatment and are influenced

by various factors such as the treatment plan, HCV-GT/subtype,

and endemic characteristics. While there are no standardized tests

for investigating HCV-RAS, Sanger dideoxynucleotide sequencing-

based approaches are generally reliable, even though their

sensitivities range from 10% to 25%. However, new generation

sequencing techniques are more sensitive and can detect variants

with a prevalence of 1%, despite some ongoing debate about the

clinical significance of variants at this level.