Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children. (8th January 2019)

• Record Type: Journal Article
• Authors: Muenchhoff, Maximilian; Adland, Emily; Roider, Julia; Kløverpris, Henrik; Leslie, Alasdair; Boehm, Stephan; Keppler, Oliver T; Ndung'u, Thumbi; Goulder, Philip J R
• Is Part Of: Journal of infectious diseases. Volume 219:Number 9(2019)
• Page Start: 1407
• Page End: 1417
• Publication Date: 2019-01-08
• Subjects: antiretroviral therapy -- cytomegalovirus -- HIV -- tuberculosis; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy668
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Susceptibility to coinfections in human immunodeficiency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell responses in children before and after ART. Methods: We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)-specific T-cell responses before and 1 year after initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays after in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation. Results: We observed differential, pathogen-specific changes after 1 year of ART in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased programmed cell death 1 (PD-1) expression. The proliferative capacity of HIV- and PPD-specific responses increased after 1 year of ART. Of note, the recovery of CMV- and TB-specific responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively). Conclusions: Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. The PD-1 pathway represents a potential target for immunotherapy in HIV-infected patients on ART with insufficient immune reconstitution. Abstract : Immune activation, immune exhaustion, and T-cell responses were studied in HIV-infected children before and after 1 year of ART. Changes in T-cell functionality were observed that differed by pathogen-specificity and were correlated with alterations of PD-1 expression and memory phenotype.