Persistent subclinical immune defects in HIV-1-infected children treated with antiretroviral therapy. (10th September 2015)

• Record Type: Journal Article
• Authors: van den Heuvel, Diana; Driessen, Gertjan J.A.; Berkowska, Magdalena A.; van der Burg, Mirjam; Langerak, Anton W.; Zhao, Dan; Charif, Halima; Hartwig, Nico G.; van Rossum, Annemarie M.C.; Fraaij, Pieter L.A.; van Dongen, Jacques J.M.; van Zelm, Menno C.
• Is Part Of: AIDS. Volume 29:Number 14(2015)
• Publication Date: 2015-09-10
• Subjects: antiretroviral therapy -- B-cell memory -- CD4+ T-cell memory -- CD8+ effector T cell -- perinatal HIV infection -- persistent immune defects -- Vγ9+Vδ2+ T cells; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000765
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objectives: With the introduction of combined antiretroviral therapy (cART), HIV-infected children can reach adulthood with minimal clinical complications. However, long-term HIV and cART in adults are associated with immunosenescence and end-organ damage. Long-term consequences of HIV and cART in children are currently unknown. Design and method: We studied 69 HIV-infected children and adolescents under cART (0–23 years) for the occurrence of subclinical immunological aberrations in blood B and T cells, using detailed flow cytometric immunophenotyping and molecular analyses. Results: Children with undetectable plasma HIV viral loads for more than 1 year showed near-normal to normal CD4 + T-cell numbers and near-normal numbers of most class-switched memory B cells. Furthermore, expansions of aberrant CD21 low B cells contracted in patients with virus suppression. In contrast, CD8 + effector T cells were increased, and CD4 + memory T cells, Vγ9 + Vδ2 + T cells and CD27 - IgA + memory B cells were decreased and did not normalize under ART. Moreover, Vγ9 + Vδ2 + T cells showed defects in their T-cell receptor repertoire selection. Conclusion: Our results show the effectiveness of current cART to enable the build-up of phenotypically diverse B-cell and T-cell memory in HIV-infected children. However, several subclinical immune abnormalities were detected, which were partially caused by defective immune maturation. These persistent abnormalities were most severe in adolescents and therefore warrant long-term follow-up of HIV-infected children. Early identification of such immune defects might provide targets for monitoring future treatment optimization. Abstract : Supplemental Digital Content is available in the text