Whole-Genome Sequencing–Based Characterization of HIV-1 in a Tertiary-Care Hospital in Mexico: Drug-Resistance Mutations and Genetic Diversity

Human immunodeficiency virus type 1 exhibits extensive genetic diversity, which has important implications for transmission dynamics, disease progression, and the effectiveness of antiretroviral therapy. In Mexico, molecular surveillance has largely relied on partial pol gene sequencing, limiting the detection of recombination events and resistance mutations outside canonical regions. In this study, we performed near-full-length whole-genome sequencing of HIV-1 from 40 treatment-naïve adults receiving care at a tertiary-care hospital in Mexico to characterize drug-resistance mutations, viral genetic diversity, and recombinant forms. Viral RNA was extracted from plasma and sequenced on an Illumina platform, followed by bioinformatic processing and interpretation using the DeepChek pipeline for subtype classification, recombinant profiling, and identification of drug-resistance mutations. Drug-resistance mutations were identified in 6/40 (15.0%) participants. NNRTI-associated DRMs were identified in 2/40 patients (5.0%), whereas NRTI- and protease inhibitor-associated DRMs were each identified in 1/40 patient (2.5%). In addition, accessory INSTI-associated substitutions were detected in 2/40 patients (5.0%). No statistically significant differences were observed between patients with and without DRMs with respect to age, sex, or plasma viral load. Furthermore, DRMs were distributed across all recombinant categories, with no significant association between recombinant profile and DRM presence (p = 0.97). Non-B subtypes and recombinant forms predominated (82.5%), while subtype B accounted for 17.5% of cases. Extensive intergenic recombination was observed, with discordant subtype assignments across gag, pol, and env regions, consistent with mosaic viral genomes. Multiple circulating recombinant forms, including CRF03_AB, CRF07_BC, CRF28_BF, and CRF39_BF, were identified, alongside a predominance of BF-related recombinants. In addition, several unique recombinant forms with complex mosaic structures were detected, reflecting ongoing recombination and viral evolution. These findings highlight the high genetic complexity of HIV-1 in this population, characterized by a predominance of recombinant forms and extensive genomic mosaicism. The detection of DRMs across diverse genetic backgrounds supports the value of baseline resistance testing and suggests that broader genomic surveillance may improve HIV-1 molecular epidemiology monitoring in Mexico.