Evaluation of A Phylogenetic Pipeline to Examine Transmission Networks in A Canadian HIV Cohort.

Lauren Mak,Jingni He,Pathum Kossinna,Raynell Lang,Quan Long,Deshan Perera,Guido Van Marle,M John Gill

doi:10.3390/microorganisms8020196

Lauren Mak, Jingni He + Show 6 more

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https://doi.org/10.3390/microorganisms8020196

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Abstract

Modern computational methods using patient Human Immunodeficiency Virus type 1 (HIV-1) genetic sequences can model population-wide viral transmission dynamics. Accurate transmission inferences can play a critical role in the characterization of high-risk transmission clusters important for enhanced epidemiological control. We evaluated a phylogenetics-based analysis pipeline to infer person-to-person (P2P) infection dates and transmission relationships using 139 patient HIV-1 polymerase Sanger sequences curated by the Southern Alberta HIV Clinic. Parameter combinations tailored to HIV-1 transmissions were tuned with respect to inference accuracy. Inference accuracy was assessed using clinically confirmed P2P transmission patient data. The most accurate parameter settings correctly inferred 48.56% of the P2P relationships (95% confidence interval 63.89–33.33%), slightly lower than next-generation-sequencing methods. The infection date was correctly inferred 43.02% (95% confidence interval 49.89–35.63%). Several novel unsuspected transmission clusters of up to twelve patients were identified. An accuracy trade-off between inferring transmission relationships and infection dates was observed. Using clinically confirmed P2P transmission data as benchmark, our phylogenetic methods identified sufficient P2P transmission relationships using readily available low-resolution Sanger sequences. These approaches may give valuable information about HIV infection dynamics within a population and may be easily deployed to guide public health interventions, without a need for next generation sequencing technology.

Highlights

The identification and testing of groups at high risk for Human Immunodeficiency Virus (HIV) infection, combined with successfully engaging Persons Living with HIV (PLWH) in combination Anti-Retroviral Therapy is critical in controlling the HIV epidemic
The HIV sequences used for analysis consisted of the HIV polymerase region and were collected through Sanger sequencing as part of routine genotypic antiretroviral drug resistance testing (GART)
When we looked back at the data captured in the clinic database for these patients, there are public health contact and blood transfusion trace back indicators that would support that these are likely credible transmission relationships

Summary

Introduction

The identification and testing of groups at high risk for Human Immunodeficiency Virus (HIV) infection, combined with successfully engaging Persons Living with HIV (PLWH) in combination Anti-Retroviral Therapy (cART) is critical in controlling the HIV epidemic. Characterisation of high-risk transmission groups can inform prevention programmes and offer cost-effective intervention strategies [3,4,5,6]. Assessing if the infection dynamics in a population is driven by a small number of individuals with repetitive high-risk behaviour or by a larger population with lower frequency risk events allows for the implementation of better-targeted public health interventions and policies. This could be done at a population level without necessarily having to identify specific individuals, thereby minimizing concerns around privacy and marginalization. Using HIV sequence data, transmission relationships can be computationally inferred through phylogenetic methods, which compare the genetic similarity of viral sequences to determine the connectivity of HIV transmission in a population [9,10,11]

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