Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease

Background: There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined. Methods: PD-1 was measured longitudinally in a cohort of recently HIV-infected individuals (n = 121) who started ART early (<6 months after infection) vs. later (>= 2 years after infection). PD-1 was also measured cross-sectionally in a diverse cohort of chronically HIV-infected adults (n 206). Results: PD-1 expression levels were high on CD8(+) T cells during early HIV infection. PD-1 levels increased on both CD4(+) and CD8(+) T cells populations in those who delayed therapy (11 and 10%/year, respectively). PD-1 levels declined and were similar in those treated early vs. late after 1 year of ART. In both cohorts, PD-1 expression on CD4(+) T cells was associated with CD4(+) T-cell activation (CD38(+)HLA-DR+) and inversely with CD4(+) cell count. In contrast, PD-1 expression on CD8(+) T cells was most strongly associated with CD8(+) T-cell activation and with plasma viral load in viremic individuals. Conclusion: Across two large cohorts of untreated and treated individuals, we found consistent associations between HIV RNA levels, CD8(+) T-cell activation and PD-1 expression on CD8(+) T cells. In contrast, CD4(+) T-cell counts and CD4(+) T-cell activation were more consistent correlates of PD-1 expression on CD4(+) T cells. PD-1 expression appears to be driven by both direct antigen and homeostatic pathways. (C) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins