Naive CD8^low T cells are prevalent in untreated HIV-infected human progressors. Cryopreserved PBMCs of HIV-negative and HIV-infected subjects in various stages of disease progression, viral control, and treatment were analyzed for cell-surface expression of the CD8α and CD8β chains in the naive pool of CD8⁺ T cells. 3 separate studies (study A, B, and C) were performed with samples from subjects of SCOPE and Options cohorts (see Table 1 and “Subjects” and supplemental Methods for more details and definitions of these groups). (A) FACS plot representing gating strategy, CD4 and CD8 expression in CD3⁺ T cells, and CD45RA and CD27 expression in CD8⁺ T cells (left to right panels). Naive (CD45RA^highCD27^high) CD8⁺ T cells are shown from a subject with progressive disease (“Prog”), from a virologically suppressed subject (“HAART”) and from a HIV-negative subject (Neg) from study A (as indicated by the blue rectangle) with measurement of CD8α expression (MdFI). (B) CD8α expression (MdFI) in naive CD8⁺ T cells in all subjects from study A. (C) CD8α (top) and CD8β (bottom) expression in naive CD8⁺ T cell in all subjects from study B. (D) Grouping strategy of subjects in study C, based on viral load (“VL”) and immune activation (“IA” measured by CD38 expression) at approximately 12 months after infection. (E) Expression of CD8α (higher) and CD8β (lower) in naive CD8⁺ T cell over time, as measured in subjects at 3 and 12 months after infection (“acute” and “chronic,” respectively) from group 1 to 3 in study C (left to right). P values were calculated using the Mann-Whitney test for group analysis as indicated by the horizontal bar (B) or compared with HIV-Neg group when not indicated (C). The paired t test was used for longitudinal follow-up of the same subject (E). When the P value is not indicated on the graph, the symbols * and ** indicate that P < .05 or P < .005 for each test, respectively.