HIV-1 genetic transmission networks among people living with HIV/AIDS in Sichuan, China: a genomic and spatial epidemiological analysis

Abstract

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.

Figure 1

Genetic transmission networks of the HIV-1 subtypes. There were 11 clusters (2.4%) for subtype B, with sizes from 2 to 5 pol sequences; 80 clusters (17.7%) for subtype CRF_08 BC, with sizes from 2 to 26 pol sequences; 18 clusters (4.0%) for subtype CRF_85 BC, with sizes from 2 to 127 pol sequences; 120 clusters (26.6%) for subtype CRF_01 AE, with sizes from 2 to 206 pol sequences; and 223 clusters (49.3%) for subtype CRF_07 BC, with sizes from 2 to 342 pol sequences.

Figure 2

Map of heterogeneities in HIV transmission routes, represented by the Pielou Index. A smaller value of the Pielou index represents more homogeneous routes of HIV transmission within a given city, while a larger value of the Pielou index represents more heterogeneous routes of HIV transmission.

Figure 3

Spatial distribution and significant spatial clusters of the phylogenetic clustering rates of HIV-1 subtypes. A smaller (larger) value represents the lower (higher) phylogenetic clustering rate, while a larger value represents the higher phylogenetic clustering rate.

Figure 4

Intensity matrices of HIV-1 transmission links between cities in Sichuan (intensity matrices). The color of the grid cell at the intersection of two cities represents the number of linkages between the people living with HIV (PLWH) in two cities. A base-10 logarithmic color bar was used to enhance contrast.

Figure 5

Flow map of intensity of HIV transmission linkages observed in the HIV-1 genetic transmission networks between cities in Sichuan. Each line represents the HIV transmission linkage between two cities, with each color of the line representing a different HIV-1 subtype and with the thickness of the line representing the number of linkages between the PLWH in two cities.