Genotypic drug resistance characteristics and their clinical guiding value in people living with HIV

Objective Genotypic drug resistance testing plays a critical role in guiding antiretroviral therapy (ART) for people living with HIV (PLWH). However, current studies lack a stratified quantitative framework to evaluate its clinical utility, which hinders the precise translation of resistance data into routine practice. Methods In this study, 274 PLWH who underwent HIV genotypic drug resistance testing were enrolled to characterize drug resistance profiles, subtype-specific resistance heterogeneity, resistance transmission clusters, and metabolic features, with particular emphasis on grading the clinical utility of genotypic resistance. Results The overall drug resistance rate was 24.09%, predominantly involving non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs). The three major locally circulating recombinant subtypes showed distinct resistance spectra and active transmission of resistant strains, whereas subtype-specific metabolic variations were confounded by demographic and immunological factors rather than resistance mutations. Notably, graded genotypic resistance guidance values were closely associated with clinical outcomes: stronger guidance values corresponded to better virological suppression and CD4 recovery, whereas weaker guidance values were associated with poorer prognosis. Conclusions This stratified evaluation framework improves the interpretation of genotype-phenotype discordance in resistance assessment, helps refine standardized resistance evaluation criteria, supports individualized ART decision-making, and provides real-world evidence for optimizing clinical management strategies and targeted HIV treatment policies.