Pre-treatment HIV-1 drug resistance spectrum and molecular transmission network characteristics in Zhejiang Province, 2023: implications for targeted control of drug-resistant HIV transmission.

چکیده اصلی

OBJECTIVE: To characterize the epidemiology, subtype distribution and transmission dynamics of pre-treatment drug resistance (PDR) among newly diagnosed antiretroviral therapy (ART)-naive individuals with human immunodeficiency virus type 1 (HIV-1) in Zhejiang Province, Eastern China, in 2023. METHODS: In this province-wide cross-sectional molecular epidemiological study, the HIV-1 pol gene was amplified and Sanger-sequenced. Genotypic resistance was interpreted using the Stanford HIV Drug Resistance Database, subtypes were assigned by phylogenetic analysis, and transmission networks were inferred at a pairwise genetic distance threshold of 0.01 substitutions/site, with sensitivity analysis across 0.001-0.015 substitutions/site thresholds. RESULTS: Among 3466 valid pol sequences, 241 PDR cases were identified, yielding an overall PDR prevalence of 6.95% [95% confidence interval (CI): 6.11%-7.80%], with the highest prevalence observed in Jinhua (10.02%; 95% CI: 7.39%-12.65%). Of the 241 PDR cases, 10 distinct HIV-1 subtypes were detected, among which CRF07_BC (43.57%, 105/241) and CRF01_AE (38.17%, 92/241) predominated. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was most frequent (67.66%, 159/235), driven by the resistance-associated mutation (RAM) K103N/S (46.47%, 112/241); high-level resistance was highest for nevirapine (63.07%, 152/241) and efavirenz (54.77%, 132/241). Overall, 42.32% of PDR cases clustered into 51 resistance-associated transmission clusters (RTCs); 18 medium/large RTCs (≥4 individuals) carried high-level NNRTI resistance, 8 with mean pairwise distances ≤0.005 substitutions/site, suggesting high sequence homology and suggestive of close epidemiological linkage among clustered strains. CONCLUSIONS: In this study, PDR cases in Zhejiang were dominated by NNRTI resistance with substantial regional clustering, indicating putative transmission networks. Scaled-up standardized PDR surveillance, optimized first-line ART regimens and cluster-targeted interventions are urgently needed to curb resistant HIV-1 transmission and inform national HIV drug resistance policy.

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