Extension Period Aims

In September 2010, The CHARTER Extension began.  In the Extension, the CHARTER aims were further refined to focus on how extended follow-up of a select number of CHARTER participants could provide further insight into the effects of low-level viral replication in the CNS, predictors of neurocognitive and neuroimaging worsening, and the reversibility of nerve injury in the context of ART.

Specific Aim 1: To explore the longitudinal neurological consequences of disproportionate HIV replication in the nervous system.

Hypothesis: Participants with evidence of disproportionate HIV replication in the nervous system (defined as viral loads in CSF that are at least as high as those in plasma) will be more likely to have progressive neurological disease (as determined by neuropsychological testing and neuroimaging) than participants who do not have disproportionate HIV replication in the nervous system.

Specific Aim 2: To examine cases that are receiving ART and undergoing cognitive decline or increasing white matter abnormalities based on neuroimaging in order to determine predictors of neurological injury.

Hypothesis:  In participants on ART, those having more evidence of white matter injury will have greater decline in neuropsychological functioning than those without any evidence of white matter injury. For our purposes, indicators of white matter injury include:  increased volume of abnormal white matter signal and white matter volume loss on structural MRI; altered diffusion along fibre tracts, such as reduced fractional anisotropy, measured with diffusion tensor imaging (DTI); and changes in metabolite concentrations that may reflect injury in white matter, such as reduced N-acetylaspartate (NAA) or increased choline (Cho), determined by MR spectroscopy.

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