Longitudinal analysis of total CD4⁺ and CD8⁺ T-cell phenotypes of IRIS and non-IRIS patients during ART. Characteristics of total CD4⁺ (A,C) and CD8⁺ T cells (B,D) were analyzed in PBMC samples from IRIS (red) and non-IRIS patients (blue) before as well as after 1, 3, 6, and 12 months of ART. (A-B) Activation phenotype and presence of recent thymic emigrants (RTE; in CD4⁺ T cells only). (C-D) Representation of T-cell differentiation states. T-cell differentiation subsets were defined by expression of CD45RO (“RO”), CCR7 (“R7”), and CD27 (“27”). T_NV indicates naive; T_CM, central memory; T_TM, transitional memory; T_EM, effector memory; and T_TE, terminal effector. T_CM*, T_TM*, and T_TE* represent phenotypically defined populations that are not described in the literature but that arise by this gating scheme; their activation phenotype and cytokine potential most closely resemble that of T_CM, T_TM, and T_TE, respectively; hence their nomenclature. Graphs represent interquartile ranges, median bars, as well as individual data points. Gray boxes indicate the first time point within 3 months of clinical manifestation of IRIS. Dashed lines separate pre-ART from on-ART samples. All time points were compared between patient groups (results indicated in black above bars/pies), as well as with corresponding pre-ART measurements within each patient group (results are color-coded and indicated below bars/pies). *P < .01; **P < .001; ***P < .0001.