Miranda-Solé, Carlota;
(2024)
Perinatally Acquired HIV and its Impact on Immune Activation,
Maturation and Thymic Activity.
Doctoral thesis (Ph.D), UCL (University College London).
![[thumbnail of CMS_Thesis_September2023.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/text.png) |
Text
CMS_Thesis_September2023.pdf - Accepted Version Access restricted to UCL open access staff until 1 February 2025. Download (15MB) |
Abstract
Human Immunodeficiency Virus (HIV) targets CD4+ helper T-cells, weakening the immune system and increasing the susceptibility to infections, leading to Acquired Immunodeficiency Syndrome (AIDS). Despite the established efficacy of antiretroviral therapy (ART) in managing HIV, the disease continues to be a substantial global health issue, with over 84.2 million infections and 40 million AIDS-related deaths accounted. Children with perinatally acquired HIV (paHIV) account for nearly 15% of AIDS-related deaths. In the absence of ART, approximately 50% of children with paHIV will not survive beyond age two, and around 80% will not reach the age of five. This study investigated the impact of paHIV on the immune system, focusing on immune activation, maturation, and thymic activity. Samples from adolescents and young adults (AYA) with paHIV from the Lymphocyte Development (LD) study were compared to individuals without HIV. The LD study aimed to explore the humoral response in paHIV upon Pneumococcus immunisation. A flow cytometry analysis revealed a more mature immune phenotype and enhanced thymic output (TO) activity in individuals with paHIV. Telomere length (TL), indicative of cellular aging, was shorter in paHIV subjects, despite exposure to ART and HIV viraemia. A correlation between TO activity and TL emerged, despite independent measurement disparities. Research extended to South African children without HIV - from the Child Wellness Clinic (CWC), and the Children with HIV Early Retroviral Therapy (CHER) study at ages two and five. CWC children displayed a dynamic TL trend, with a peak at 2.5 years, parallel to both TO and naïve B-cell output (NBO) peaks. CHER children had shorter TL than the controls at two but not at five years, suggesting benefits of early ART introduction. This study sheds light on paHIV’s intricate relationship between immune responses and treatment strategies, offering insights for HIV management and patient outcomes.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Perinatally Acquired HIV and its Impact on Immune Activation, Maturation and Thymic Activity |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | HIV, paHIV, Antiretroviral Therapy, AIDS, Thymic Output, Lymphocyte Development study, Children with HIV Early Retroviral Therapy study, CHER, Telomere length |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10186250 |
Archive Staff Only
 |
View Item |
