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Objective  The 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.    Background  While 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.    Methods  We 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.    Results  HIV 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.    Conclusion  HIV 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.

Multi-scale immunoepidemiological modeling of within-host and between-host HIV dynamics: systematic review of mathematical models