Genetic Subtypes, Pretreatment Drug Resistance, and Associated Factors Among Individuals Newly Diagnosed With HIV-1 in Zhejiang Province From 2022 to 2024: Cross-Sectional Study

Abstract Background Pretreatment drug resistance (PDR) poses an increasing threat to the effectiveness of antiretroviral therapy and treatment-as-prevention strategies. Zhejiang Province, an economically developed region in eastern China with high population mobility, experiences complex HIV-1 subtype dynamics and evolving resistance patterns. However, recent population-based evidence integrating HIV genetic subtypes, PDR prevalence, and associated factors remains limited. Objective This study aimed to characterize HIV-1 subtype distribution, estimate the prevalence of PDR, and identify associated demographic, virological, and prophylaxis-related factors among newly diagnosed individuals in Zhejiang Province from 2022 to 2024. Methods We conducted a cross-sectional study among adults newly diagnosed with HIV-1 in Zhejiang Province between 2022 and 2024. Demographic, epidemiological, laboratory, and exposure prophylaxis information was collected through the provincial HIV surveillance system. Partial Pol gene sequences were amplified and sequenced to determine HIV subtypes and drug resistance mutations. PDR was interpreted using the Stanford University HIV Drug Resistance Database. Logistic regression models were applied to identify factors associated with PDR. Results Among 8798 newly diagnosed individuals, the predominant subtypes were CRF07_BC (n=3913, 44.5%), CRF01_AE (n=2524, 28.7%), and CRF08_BC (n=954, 10.8%), with significant heterogeneity across age groups, sexes, transmission routes, and diagnosis years ( P <.001). Overall PDR prevalence was 5.7% (n=504), with resistance mainly to nonnucleoside reverse-transcriptase inhibitors (n=352, 4.0%). The most frequently detected mutations were K103N, M184V, and M46L. Multivariable analysis showed that higher baseline CD4 cell counts, diagnosis in 2023 and 2024, and infection with the CRF01_AE subtype were independently associated with increased odds of PDR. Pre-exposure prophylaxis was not associated with overall PDR; however, drug-specific analyses demonstrated significant associations between exposure prophylaxis and pretreatment resistance to emtricitabine ( P <.001) and lamivudine ( P <.001). Conclusions HIV-1 genetic diversity in Zhejiang Province remains complex and dynamic, accompanied by an increasing prevalence of PDR. Although exposure prophylaxis was not linked to overall PDR, its association with emtricitabine-specific resistance highlighted the need for strengthened HIV-1 testing prior to prophylaxis initiation and enhanced resistance surveillance, but they require confirmation in future studies.