HIV Infections Clinical Trial
Official title:
Role of Naive T-Cells in the Pathogenesis of T-Cell Decline and Long Term Persistence of HIV
While HIV mainly infects mature T-cells it can also infect newly produced (or naïve) T-cells. These infected naïve T cells may then act a viral reservoir even in patients with undetectable viral loads. Understanding when and how these cells are infected is important because it could help us to understand why patients fail therapy even if they have a persistently undetectable viral load.
The overall goal of this project is to provide a comprehensive analysis of the role of naïve
T-cells in the pathogenesis of T-cell decline and long-term persistence of HIV infection.
The study is divided into two parts.
Part 1 aims to determine the origin of HIV infected naïve T-cells in vivo by assessing the
viral relatedness between HIV strains from naïve and memory CD4 T-cells. To do this we will
be studying ten chronically infected individuals. Naïve and memory CD4 T-cells from these
individuals will be purified using a magnetic bead sorting (MACS) strategy. Envelope
sequences will then be isolated and subjected to diversity calculation
Part 2 seeks to answer whether infection of naïve T-cells is established early in infection
and what the effect of antiretroviral therapy is on this subset of T-cells. We will
initially examine the relative proportion of CD31+ (recent thymic emigrants) and CD31- naive
CD4+ T-cells in infected acute (n=15) and chronic (n=15) infection and uninfected (n=15)
individuals compared with healthy controls. We will then prospectively test individuals
prior to and at 3, 6, 12, 18 and 24 months following intiation of HAART (Highly Active
Antiretroviral Therapy) in individuals with acute (n=10) and chronic (n=10) HIV infection.
Immunophenotyping will detemine the proportion of naïve T-cells that are CD31+ and those
that are CD31-. Naïve and memory T-cell subsets will again be purified and total and
integrated HIV DNA will be quantified using real-time PCR.
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Observational Model: Defined Population, Time Perspective: Longitudinal
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