Increased Immune Activation and Exhaustion in HIV-infected Youth. Issue 12 (December 2016)

• Record Type: Journal Article
• Authors: Eckard, Allison Ross; Rosebush, Julia C.; Lee, S. Thera; O'Riordan, Mary Ann; Habib, Jakob G.; Daniels, Julie E.; Labbato, Danielle; Uribe-Leitz, Monika; Chahroudi, Ann; McComsey, Grace A.
• Is Part Of: Pediatric infectious disease journal. Volume 35:Issue 12(2016)
• Publication Date: 2016-12
• Subjects: HIV -- immune activation -- immune exhaustion -- pediatrics; Communicable diseases in children -- Periodicals; Infection in children -- Periodicals; 618.929
• DOI: 10.1097/INF.0000000000001326
• Languages: English
• ISSNs: 0891-3668

Abstract

Abstract : Background: Immune activation and exhaustion drive several comorbidities and disease progression in HIV-infected adults; however, they are not well studied in HIV-infected youth. Thus, this study sought to examine levels of immune activation and exhaustion in this population, investigate associated HIV- and non-HIV-related variables and compare results with a matched healthy control group. Methods: HIV-infected youth 8–25 years of age on stable antiretroviral therapy with an HIV-1 RNA level <1000 copies/mL were enrolled, along with matched healthy controls. We measured T-cell and monocyte immune activation and exhaustion markers in cryopreserved peripheral blood mononuclear cell and plasma samples. Results: A total of 136 subjects (80 HIV+: 66% male; 91% black) were enrolled. Markers of CD4+ and CD8+ T-cell activation were higher in the HIV-infected group versus controls [mean % CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ = 2.2 versus 1.5 ( P =0.002) and 4.9 versus 2.2 ( P <0.0001), respectively], as were exhausted CD4+ and CD8+ T-cells [mean % CD4+CD38+HLA-DR+PD-1+ and CD8+CD38+HLA-DR+PD-1+ = 1.0 versus 0.5 ( P <0.0001) and 1.6 versus 0.7 ( P <0.0001), respectively]. There were no differences in proportions of inflammatory or patrolling monocytes between groups ( P >0.05); however, soluble CD14 was higher in HIV-infected compared with controls (1.6 versus 1.4 µg/mL; P =0.01). Current CD4 count, low-density lipoprotein cholesterol and age were the variables most associated with CD4+ and CD8+ T-cell activation. Conclusions: CD4+ and CD8+ T-cell immune activation and exhaustion are higher in HIV-infected youth compared with matched controls, while monocyte subpopulations are not altered despite a high soluble CD14 level. The clinical significance of the increased immune activation and exhaustion should be further explored.