Increased Immune Activation and Exhaustion in HIV-infected Youth.
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.



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.



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.



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.
From the *Department of Pediatrics, Division of Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina; †Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; ‡Department of Pediatrics, Rainbow Babies and Children's Hospital/University Hospitals Case Medical Center, Cleveland, Ohio; and §Children's Healthcare of Atlanta, Atlanta, Georgia.
Allison Ross
AR
Eckard
Julia C
JC
Rosebush
S Thera
ST
Lee
Mary Ann
MA
O'Riordan
Jakob G
JG
Habib
Julie E
JE
Daniels
Danielle
D
Labbato
Monika
M
Uribe-Leitz
Ann
A
Chahroudi
Grace A
GA
McComsey
D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D055815:Young Adult