Global dynamics of HIV multi-scale model with gene therapy

Gene therapy by editing CCR5 gene is becoming an exciting alternative to antiretroviral therapy (ART), but how intra-host gene therapy will affect the spread of HIV at the inter-host scale is unknown. We aimed to propose a multi-scale HIV model coupling individual and population dynamics to evaluate the effect of gene therapy on the population-scale transmission of HIV. We constructed Lyapunov functionals to explore the global threshold behavior of multi-scale model, and obtained that the inter-host reproduction number R₀ decided whether the epidemic persisted or not. We used three kinds of data (the annual AIDS cases, AIDS deaths, and HIV prevalence) from 1980 to 2023 among men who have sex with men (MSM) in San Francisco to estimate the parameters and validate the model. Numerical simulations showed that increasing the intra-host efficacy of gene therapy and the fraction of generating gene-edited cells would be always beneficial to control the disease, but whether expanding the coverage of people using gene therapy could decrease the transmission depends on the generating capacity of gene-edited cells, and the efficacy of gene therapy and ART. These results will provide important insights on the impact of gene therapy and ART on controlling HIV infection across multiple scales.