Majekodunmi, Adedeji Oluwaseun;
(2018)
Mathematical and statistical modelling of factors affecting CD4 T cell reconstitution in HIV-infected children starting anti-retroviral therapy.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Majekodunmi_ID_thesis.pdf Download (5MB) | Preview |
Abstract
Thymic output in children increases to its peak during the first 1 year of life followed by a gradual decline to a steady state by 20 years of age. Immune reconstitution in HIV-infected children is a highly dynamic process driven by factors such as thymic output, age, proliferation and loss of T cells, viral load, anti-retroviral therapy (ART) and co-infection. Understanding the mechanisms driving immune reconstitution is critical to ensuring the best clinical outcomes in HIV-infected children and in shaping the future of medical intervention. This thesis focuses on the factors affecting the degree and extent of CD4+ T cell reconstitution in HIV-infected children receiving ART. Hepatitis C virus (HCV) co-infection in HIV-infected patients has been linked to an increased incidence of hospitalisation, rapid progression to end stage liver disease and hepatocellular carcinoma. Despite effective antiretroviral drugs, liver-related complications are now a leading cause of mortality and morbidity in HIV-infected patients. The first section of this work uses a monophasic asymptotic recovery model to investigate the impact of hepatitis C co-infection on CD4+ T cell recovery in HIV-infected children. The model was fitted to age-adjusted CD4+ T cell counts using the framework of non-linear mixed-effects regression and the effects of important covariates such as age, viral load and pre-ART hepatitis C status were investigated. The results indicate that HIV/hepatitis C co-infected children recover their CD4+ T cells much more slowly compared to HIV-monoinfected individuals. The next chapter uses the same model to identify predictors of poor immune reconstitution in 2204 HIV-infected children on ART and higher age at start of therapy was highlighted as a main factor associated with poor immune recovery. Finally, a mechanistic model of naive CD4+ T cell homeostasis was developed aiming to understand the recovery of CD4+ lymphocyte subsets in HIV-infected children receiving ART. As CD31+ T cells are an important component of naive T cell pool in children, the model was further adapted to understand dynamics of CD31+ T cell homeostasis in HIV-infected children on ART. Reduced theoretical thymic output was associated with poor CD31+ T cell recovery which is strongly related to poor overall CD4+ T cell recovery.
Type: | Thesis (Doctoral) |
---|---|
Qualification: | Ph.D |
Title: | Mathematical and statistical modelling of factors affecting CD4 T cell reconstitution in HIV-infected children starting anti-retroviral therapy |
Event: | UCL (University College London) |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science |
URI: | https://discovery.ucl.ac.uk/id/eprint/10044994 |




Archive Staff Only
![]() |
View Item |