Abstract
ObjectiveThe objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level.BackgroundWhile within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models is an emerging method to infer the synergistic dynamics of HIV at the individual and population levels.MethodsWe reviewed nine articles using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework that focused on the synergistic dynamics of HIV immunoepidemiological models at the individual and population levels.ResultsHIV immunoepidemiological models simulate viral immune dynamics at the within-host scale and the epidemiological transmission dynamics at the between-host scale. They account for longitudinal changes in the immune viral dynamics of HIV+ individuals, and their corresponding impact on the transmission dynamics in the population. They are useful to analyze the dynamics of HIV super-infection, co-infection, drug resistance, evolution, and treatment in HIV+ individuals, and their impact on the epidemic pathways in the population. We illustrate the coupling mechanisms of the within-host and between-host scales, their mathematical implementation, and the clinical and public health problems that are appropriate for analysis using HIV immunoepidemiological models.ConclusionHIV immunoepidemiological models connect the within-host immune dynamics at the individual level and the epidemiological transmission dynamics at the population level. While multi-scale models add complexity over a single-scale model, they account for the time varying immune viral response of HIV+ individuals, and the corresponding impact on the time-varying risk of transmission of HIV+ individuals to other susceptibles in the population.
Highlights
HIV prevalence and mortality were 38.8 million and 1.2 million deaths respectively in 2015, with annual incidence being relatively constant at 2.6 million per year from 2005 to 2015 (Wang et al, 2016)
The within-host scale of HIV immunoepidemiological models simulate the immune-viral dynamics of HIV, which can later be used to determine the impact on transmission between hosts
We categorize the within-host models by whether they model a single strain of HIV, super-infection, drug resistance, evolution, co-infection and therapeutic interfering particles
Summary
HIV prevalence and mortality were 38.8 million and 1.2 million deaths respectively in 2015, with annual incidence being relatively constant at 2.6 million per year from 2005 to 2015 (Wang et al, 2016). Access to big data and emergence of unanswered questions enable novel methods of mathematical models to connect within-host immune viral dynamics at the individual level, and the between-host epidemiological transmission of infectious diseases at the population level (Gog et al, 2015). Mathematical models of HIV dynamics have been extensively studied using single-scale based models at the immunological and epidemiological scales (Perelson & Ribeiro, 2013; Akpa & Oyejola, 2010). The immunological models focus on the within-host immune viral dynamics at the individual level, while the epidemiological models focus on the between-host transmission dynamics at the population level. Multi-scale immunoepidemiological modeling is an emerging method to study the synergistic dynamics of HIV at the individual and population levels (DebRoy & Martcheva, 2008; Yeghiazarian, Cumberland & Yang, 2013; Handel & Rohani, 2015)
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