Hepatitis C Virus Resistance-Associated Substitutions in Mexico.

Hepatitis C virus (HCV) is susceptible to resistance-associated substitutions (RASs) in the NS3, NS5A, and NS5B nonstructural genes, key targets of the direct-acting antivirals (DAAs). This study aimed to assess the prevalence and distribution of RASs across different HCV subtypes in Mexico. A Genbank dataset of 566 HCV sequences was analyzed. Most sequences were from Mexico City (49.1%, 278/566) and Jalisco (39.4%, 223/566). The NS5B region was the most sequenced (59.7%, 338/566). The most frequent HCV subtypes were 1a (44.0%, 249/566), 1b (28.6%, 162/566), 2b (9.5%, 54/566), and 3a (6.2%, 35/566). Subtypes 1a (57.4%, 128/223) and 3a (12.6%, 28/223) were significantly higher in Jalisco than in Mexico City (34.2%, 95/278 and 2.5%, 7/278), whereas subtype 1b was higher in Mexico City (34.5%, 96/278 vs. 14.8%, 33/223). Subtype 1a increased from 2019 to 2024, representing 49.4% (123/249) of all reported cases. RASs were detected in NS3 (6.7%, 1/15), NS5A (2.9%, 3/102), and NS5B (0.3%, 1/349), with the most frequent mutations being Q80K, Y93H, and S282T, respectively, and detected in subtypes 1b (n = 3), 1a (n = 1), and 2a (n = 1). In conclusion, Mexico's HCV sequencing-based surveillance is limited. Subtype 1a predominated, but frequencies varied across states. The prevalence of RASs varied by gene from 0.3% to 6.7%. Establishing regional sequencing centers for NS3, NS5A, and NS5B is crucial to monitoring Mexico's DAA-resistant mutations and HCV subtype genetic diversity.