CD4? T-cell deficiency and dysfunction in HIV patients receiving combination antiretroviral therapy

    Research output: ThesisDoctoral Thesis

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    Abstract

    [Truncated abstract] Failure to fully reconstitute the immune system is a common clinical problem in HIV patients who were severely immunodeficient before responding to combination antiretroviral therapy (CART). This can manifest as a deficiency in the number or function of CD4+ T-cells and occurs most often in patients who had a nadir CD4+ T-cell count below 100/μl when CART was commenced. Observational studies of large cohorts of HIV patients, such as the D:A:D study, have demonstrated that patients with low CD4+ T-cell counts have increased rates of death compared with patients who have normal CD4+ T-cell counts. Furthermore, individual case studies suggest that impaired recovery of pathogen-specific immune responses during CART is associated with opportunistic infections or disease progression. This thesis addresses possible causes of deficiencies in CD4+ T-cell number or function in HIV patients who were very immunodeficient prior to treatment and are responding (virologically) to CART. Firstly, the role of the thymus in producing naive CD4+ T-cells and the effects of persistent immune activation on the recovery of CD4+ T-cell numbers were assessed in patients with either low or high CD4+ T-cell counts after long-term CART. ... Proportions of antigen presenting cell (APC) subpopulations were examined in HIV patients with low or high CMV-specific CD4+ T-cell responses after long-term CART. HIV patients had significantly lower proportions of plasmacytoid dendritic cells (pDC) than HIV-negative controls.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2006

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