Genetic Diversity, Drug Resistance, and Molecular Transmission Networks of HIV-1 in Zunyi: Implications for Precision Prevention

Background HIV-1 genetic diversity and the spread of pretreatment drug resistance (PDR) complicate epidemic control. Southwestern China has a heterogeneous HIV epidemic, but molecular transmission dynamics in many prefecture-level settings remain poorly described. Methods We analyzed HIV-1 pol sequences from 208 newly diagnosed individuals in Zunyi, Guizhou Province. Genotypes were assigned by reference-based phylogenetic analysis; PDR was interpreted using the Stanford HIV Drug Resistance Database. Molecular transmission networks were inferred from pairwise genetic distances calculated with the TN93 model, and factors associated with PDR and clustering were evaluated using logistic regression. Results CRF07_BC (56.3%) and CRF01_AE (29.3%) were the predominant genotypes. PDR was detected in 21.2% of participants and varied significantly across genotypes, with higher prevalence observed in CRF08_BC and other recombinant forms. Molecular network analysis identified 31 transmission clusters involving 36.1% of sequences, with cluster sizes ranging from 2 to 6 nodes. Most clusters were small, and both densely connected subgraphs and simple linear chains were observed, indicating heterogeneous transmission patterns. Clustered cases were largely heterosexual and included a high proportion of individuals aged ≥ 50 years. CRF07_BC formed more tightly connected clusters, whereas CRF01_AE exhibited greater structural diversity. Multivariate analysis showed that divorced or widowed individuals were less likely to be included in transmission clusters. Conclusions The HIV epidemic in Zunyi is characterized by high genetic diversity, fragmented molecular transmission networks, and genotype-specific clustering patterns. Integrating molecular network analysis with routine drug resistance surveillance can improve understanding of local transmission dynamics and support precision HIV prevention strategies in southwestern China.