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This study assessed the prevalence, associated factors, and transmission networks of PDR among newly diagnosed, ART-na\u00efve individuals in Guangxi, China, from 2019 to 2022. A cross-sectional study was conducted between 2019 and 2022 in Nanning, Guangxi, involving 1,260 newly diagnosed, ART-na\u00efve individuals with HIV. PDR levels and mutations were identified using the Stanford HIV Drug Resistance Database. Multivariable logistic regression models were employed to identify factors associated with PDR and to cluster the molecular network. A total of 1,048 eligible pol sequences were analyzed. The overall prevalence of PDR was 8.4%, with non-nucleoside reverse transcriptase inhibitors (NNRTIs) being the most commonly affected drug class. The most prevalent NNRTI-associated mutation was E138A (2.4%). High-level resistance was primarily observed to efavirenz and nevirapine. The CRF08_BC subtype exhibited significant clustering of PDR-related sequences. Those individuals diagnosed in 2022 were more likely to have PDR. Transmission networks clustering was significantly associated with CRF01_AE and CRF08_BC subtypes, older age, and heterosexual transmission. This study identified a moderate prevalence of PDR among newly diagnosed HIV patients in Guangxi, primarily driven by NNRTI-associated resistance mutations. The pronounced clustering of PDR in the CRF08_BC subtype highlights the need for subtype-specific surveillance and intervention strategies. To improve treatment outcomes and constrain the spread of resistance, targeted educational programs on ART adherence and drug resistance awareness should be prioritized, especially among older adults and individuals infected through heterosexual contacts, alongside enhanced molecular monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>This study highlights the growing challenge of pretreatment drug resistance (PDR) among newly diagnosed individuals with HIV in Nanning City. As antiretroviral therapy (ART) coverage expands, the persistence and transmission of drug-resistant strains pose a significant barrier to long-term treatment success. By documenting trends in PDR and identifying associated factors within a large representative sample, this study offers timely and actionable insights for clinicians and public health policymakers. The identification of key resistance mutations and clustering patterns, particularly in the CRF08_BC subtype, provides a critical foundation for tailored intervention strategies. Overall, these findings address a significant regional data gap and contribute to the optimization of HIV treatment and prevention efforts in China.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03149-24","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T13:02:44Z","timestamp":1757682164000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Molecular epidemiology and pretreatment drug resistance of HIV-1 among newly diagnosed individuals in Nanning City, Guangxi, China"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9603-9084","authenticated-orcid":false,"given":"Ting","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dveyr97","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical 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