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Title: The influence of human immunodeficiency virus and early antiretroviral therapy on the immunology and virology of infants and children
Author: Payne, H. A.
ISNI:       0000 0004 8497 8494
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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In children infected with human immunodeficiency virus (HIV) CD4 T-cell loss results in profound immunodeficiency and susceptibility to infection, however loss of CD4 Tcells can be partially reversed by antiretroviral therapy (ART). Although the Children with HIV Early Antiretroviral Therapy (CHER) trial demonstrated significant reduction in morbidity and mortality from early ART among South African infants, the immunological and virological mechanisms by which this survival advantage occurs are not completely understood. The work described here used stored specimens of peripheral blood mononuclear cells and plasma from HIV-infected children in CHER and HIV-uninfected children from the Child Wellness Clinic, a cross-sectional study of healthy South African children. The overall aims were to explore the influence of HIV and ART on immunophenotypes, thymic and naïve B-cell output, HIV serostatus and HIV proviral DNA. The main outcomes included: development of haematological and immunological reference ranges for South African children; and an observation of a naïve/memory T-cell ratio of 1:1 within the first decade of life in South African children compared with the third decade in industrialised countries. Trajectories of thymic and naïve Bcell output were created for healthy South African children. Overall early ART sustained thymic output and increased naïve B-cell output in CHER participants compared to healthy controls. Higher CD4 counts were significantly associated with increased thymic output, and deferred/interrupted ART or poor clinical outcome were associated with lower thymic and naïve B-cell output. Early ART and continuous HIV RNA suppression reduces HIV proviral DNA, however despite adequate viral suppression, immunological disturbances persist. Finally, almost half children receiving early ART were HIV-antibody seronegative by 2 years. These insights develop understanding of the interplay between the immunology and virology of HIV-infected children on ART, and could support further research to advance ART-strategies and optimise the immunological fitness and clinical health of HIV-infected children.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available