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Applying phylogenetic lineage-level diversification rate to infer epidemiological risk factors and spatiotemporal distribution of HIV transmission in British Columbia McLaughlin, Angela


Background Despite the widespread availability of antiretroviral therapy, sub-populations are burdened by disproportionately high HIV transmission within both developed and un-developed countries. By identifying groups and areas where people are at a higher risk of HIV transmission, we can better target interventions to those communities. Phylogenetic analysis of HIV genetic sequences generated from resistance testing for people living with HIV can augment traditional epidemiological methods to quantify transmission. Each virus’ branching rate in the phylogenetic tree, referred to as its lineage-level diversification rate, is an estimate of its transmission rate. Methods The viral diversification rate was calculated for 36,271 partial pol HIV sequences representing 9,310 participants in the British Columbia Drug Treatment Program between May 1996 and March 2018. First, the relationships between patient-level diversification rate with age, viral load, health authority, risk behavior, ethnicity, and clinical background were explored using a generalized linear model. Subsequently, patient data was aggregated according to their census tract of residence in order to build a community-level zero-inflated negative binomial model to predict new HIV cases. Results At the patient level, high HIV diversification rate was positively associated with being younger, reporting injection drug use, having co-infection with hepatitis C virus, having a high most recent viral load, and residing within the Northern BC Health Authority, while having ever had AIDS and identifying as black were both significantly associated with lower diversification rates. At the census tract level, the sum of patients’ annual change in diversification rate improved the specificity, accuracy, and correlation of observed and predicted values of a model to predict new HIV cases relative to a model including only epidemiological and clinical patient data. Conclusions Analyzing the distribution of phylogenetic HIV diversification rate among people living with HIV in BC corroborated known risk factors for transmission and revealed areas at risk of new infections. This tool could be useful for public health surveillance and serves as proof of principle that phylogenetics could further inform the allocation of harm reduction services while still maintaining patient confidentiality.

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