Abstract
BACKGROUND: Aksu Prefecture is among the regions most heavily affected by HIV-1 in China, yet data on acquired drug resistance (ADR) among antiretroviral therapy (ART)-treated individuals with virologic failure remain limited. This study aimed to characterize the prevalence, mutation patterns, and genetic clustering of drug resistance mutations (DRMs) in Aksu. METHODS: We conducted a retrospective study among ART-treated individuals with virologic failure in Aksu Prefecture from 2022 to 2023. HIV-1 pol sequences were obtained from 675 individuals to identify DRMs. Genetic networks were constructed to assess clustering among individuals harboring DRMs (n = 407). Univariable and multivariable logistic regression analyses were used to identify factors associated with DRMs clustering. RESULTS: The prevalence of ADR was 56.9% (384/675). CRF07_BC was the predominant subtype (97.6%). The most common DRMs were K103N/S (60.7%), M184V/I (27.3%), G190A/E/S (11.3%), and E138A/K/Q/G (10.8%), conferring high-level resistance mainly to lamivudine (3TC), efavirenz (EFV), and nevirapine (NVP). K65R was more frequent among individuals receiving TDF + 3TC + EFV/NVP, whereas Q58E was more common among those receiving LPV/r + 3TC + TDF/AZT (both p < 0.05). Genetic network analysis showed that 34.2% (139/407) of individuals with DRMs formed clusters. Higher viral load was associated with clustering, whereas LPV/r-based regimens were associated with a lower likelihood of clustering. CONCLUSION: HIV-1 ADR remains highly prevalent among ART-treated individuals with virologic failure in Aksu. Extensive resistance to NNRTIs was observed, whereas susceptibility to LPV/r was largely preserved. The clustering of DRMs underscores the importance of molecular surveillance for guiding targeted interventions. These findings support accelerating access to effective second-line regimens, strengthening pretreatment resistance surveillance, and prioritizing adherence support among central individuals with high viral loads.