Fig 1. Scheme for the model-based analysis of the effect of PD-L1 blockade on CD4 T cell and virus load quasi-steady states for diverse HIV infection phenotypes.

(A) Analysis scheme for HIV-specific CD8 T cell proliferative responsiveness towards PD-L1 blockade. Two assumptions are implemented to estimate separately the effect on turnover rates and change of specific T cell precursor frequencies. (B) Prediction scheme for the effect of the PD1-induced proliferative responsiveness on different HIV phenotypes based on a model for CTL-mediated HIV control. HIV phenotypes are based on CD4 T cell counts, virus load and progression rates [18]. For each phenotype, a range of underlying mechanisms is hypothesized and connected to the model parameters virus elimination rate c (H1), total number of virus particles produced per infected cell N (H2), the total influx of un-infected CD4 T cells s (H3) and the infection rate k (H4). Hypothesis 5 (H5) considers s and c. (C) Definition of HIV infection phenotypes [18]. P-HVL, progressors with high viral load; P-MVL, progressors with medium viral load, P-VC, progressors, viral controllers; SP-VC, slow progressors, viral controllers; SP-HIC, slow progressors, HIV controllers; LTNP-HIC, long-term nonprogressors, HIV controllers. The predicted change in CD4 T cell counts for the range of phenotypes and different hypotheses is shown in green as an example based on the proliferative responsiveness of donor 156.