Background: Spatialized HIV genetic transmission networks can help understand dynamic changes of HIV-1 at the regional level. This study aimed to combine genomic, epidemiological, and spatial data to investigate the patterns of the HIV-1 epidemic at both individual and regional levels among people living with HIV (PLWH) with virological failure of antiretroviral therapy (ART).
Methods: We evaluated the transmission patterns of 5,790 PLWH with identified pol sequences of the five main HIV-1 subtypes (B, CRF08_BC, CRF85_BC, CRF07_BC, and CRF01_AE) in Sichuan Province, China. A phylogenetic cluster was defined as a group of sequences with genetically similar HIV strains, with all phylogenetic clusters forming an HIV-1 genetic transmission network for each subtype. Logistic regression was used to identify the potential risk factors for phylogenetic clustering. Spatial analysis was applied to demonstrate the geographic patterns of phylogenetic clustering rates; intensity matrices and flow maps were made to demonstrate the intensity of transmission within and between cities.
Findings: There were 2,159 (37.3%) of 5,790 PLWH, distributed in 452 phylogenetic clusters. Some individual clinical and behavioral factors were associated with phylogenetic clustering, including a viral load of >50,000 copies/ml (OR=1.16, 95%CI=1.02-1.33), infection of other sexually transmitted diseases (OR=1.38, 95%CI=1.12-1.69), and ≥5 non-marital sexual partners (OR=1.25, 95%CI=1.03-1.51), while >3 years of treatment since the initial ART was associated with less likelihood of phylogenetic clustering (OR=0.82, 95%CI=0.70-0.97). The phylogenetic clustering rates varied regionally and were highest in the central region of Sichuan, especially for subtype CRF08_BC. The significant spatial clusters of high and low phylogenetic clustering rates were detected in the east (Dazhou for B; Zigong and Luzhou for CFR08_BC) and west (Yaan and Ganzi for CRF07_BC), respectively. The proportion of intercity transmission varied across cities from 0.14 (Yibin) and 1.00 (Ganzi). Stronger intercity transmission than average existed between some cities, e.g., between Deyang and Neijiang. CRF07_BC was the most widespread subtype between cities, and CRF85_BC (a novel HIV-1 subtype) showed strong intercity transmission (e.g., between Yibin and Guangan).
Interpretation: The phylogenetic clustering rates and intercity connections of HIV-1 have varied geographically, possibly due to varying human mobility, traffic convenience, and economic activities. Our findings enhanced the understanding of the dynamics of HIV-1 transmission from individual to city level, and demonstrated a novel cross-disciplinary (epidemiological, genetic, and spatial) approach by which we identified high-risk populations and areas. Our approach could be adapted to other regions for precision public health interventions.
Funding: The National Natural Science Foundation of China, Sichuan Science and Technology Program, Project of Sichuan Provincial Health Committee, Science and Technology Project of Sichuan Provincial Health Committee, Wuhan University 351 Talent Program, 2020, and the International Institute of Spatial Lifecourse Epidemiology (ISLE).
Keywords: HIV; genetic epidemiology; genetic transmission network; spatial analysis; spatial epidemiology.
© 2021 The Author(s).