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.

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.