Drug Resistance Among Newly Diagnosed People Living with HIV-1 in Sichuan, China: A Large-Scale Population-Based Cross-Sectional Study.

Introduction: The increasing utilization of antiretroviral (ART) medications by people living with HIV(PLWH) poses a potential risk to the efficacy of standardized ART management protocols in resource-limited settings, particularly as it may accelerate the emergence of transmitted drug resistance (TDR). Our research aimed to elucidate the prevalence, risk factors, geographical variations, and transmission patterns of TDR to inform and enhance ART management strategies. Methods: The study covered newly diagnosed PLWH in Sichuan from July 2022 to June 2023. We conducted sequencing - based resistance profiling and then analyzed TDR via the Stanford HIV Drug Resistance Database and logistic regression to identify associated factors via SPSS. ArcGIS and spatial statistics were used to create LISA maps showing the TDR distribution. HIV-TRACE's Tamura Nei 93 model was used to assess genetic clustering, and QGIS was used to analyze TDR intensity within and between cities. Results: This study found that the prevalence of TDR in Sichuan had reached a moderate level, with a resistance rate of 10.91%. Resistance varied by drug class: 8.08% for NNRTIs, 1.34% for NRTIs, and 2.22% for PIs. Regions like LS, DY, SN, and LZ had higher TDR rates. Within NNRTIs, efavirenz (EFV) and nevirapine (NVP) resistance rates were 6.26% and 6.50%, respectively. Furthermore, risk factors for TDR included age under 15, HIV-1 subtypes, and residing in areas with high ART failure rates. In addition, spatial analysis showed significant clustering of TDR, especially for PIs and NNRTIs, with hotspots identified in certain regions. Among 1,486 drug-resistant PLWH, 52.76% formed resistance-linked networks, comprising 181 molecular clusters. Key resistance mutations included K103N, E138A, V179D, Y181C, and Q58E. The transmission intensity of TDR varied across regions, highlighting complex spatial dynamics. Discussion: The prevalence of TDR in Sichuan had reached moderate epidemic levels, with certain cities already experiencing high epidemic rates. It is urgent that we urgently expand targeted genotypic drug resistance detection and implement interventions to improve medication adherence.