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Title: Mechanisms of non-progressing paediatric HIV-1 infection
Author: Adland, Emily
ISNI:       0000 0004 6498 0802
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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HIV-infected children progress more rapidly to AIDS than adults and, in sub-Saharan Africa, without antiretroviral therapy (ART), more than 50% will die before their second birthday. However, a minority of perinatally infected children will become paediatric non-progressors (PNP). The reasons for this rapid disease progression and the immunological correlates of protection against rapid progression are incompletely understood. This thesis focuses principally on paediatric HIV infection, and addresses the immunological and viral influences on disease progression. This work shows that Human Leukocyte Antigen (HLA) class I variation does not significantly influence progression rates in paediatric HIV infection, in stark contrast to adult HIV infection where HLA class I allele variation substantially impacts disease progression. This study describes potent broadly neutralizing antibody responses along with strong virus-specific T-cell activity in HIV-infected children. These virus-specific immune responses, however, do not protect against progression. The primary driver of non-progression in HIV infected children is low levels of T cell immune activation despite persistently high viraemia. This suggests close similarities with mechanisms evolved over thousands of years of non-pathogenic SIV infection in non-human primates. Further evaluation of the mechanisms underlying paediatric non-progression is relevant both to reaching a better understanding of HIV pathogenesis and to underpin future HIV cure strategies.
Supervisor: Goulder, Philip Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available