Approximately one quarter of AIDS patients develop severe cognitive deficits called HIV-associated dementia complex. With the advent of """"""""triple drug"""""""" therapy, it is unclear whether treatment of systemic viral burden will lead to an increased or decreased incidence of neurologic disease. There is some controversy regarding the importance of viral burden in mediating neurologic disease. With the advent of the RNA assays for viral burden in serum, several groups have examined whether this technique could be used for measuring viral burden in tissues. As reported in the investigators' Preliminary Results section, they believe that their pilot study using their bank of AIDS brain tissues shows substantial promise to quantify brain viral burden with minimal subjective interpretation, using a branched-DNA test. The investigators propose three Specific Aims; # 1: Compare branched-DNA assessment of brain viral burden to previously utilized assays. Results from this study will permit assessment of how the newer detection assay compares to that used over the previous decade. # 2: Expand the viral burden assessment to include the following regions: caudate, putamen, thalamus, hippocampus, substantia nigra, cerebellum and when available, spinal cord. Data from this specific aim will test the hypothesis of whether there is early or more abundant infection of specified regions of the CNS. # 3: The branched DNA test will be used to assess HIV RNA copy number per mL of post-mortem CSF and per milligram of post-mortem spleen tissue to compare these values to overall brain tissue viral burden. These studies aim to show how well viral burden in other body compartments compares to the brain and will test the hypothesis that the CSF may be used as a surrogate marker of brain viral burden. Additionally, these studies aim to begin to assess the relationship between treating systemic viral burden and its relationship to brain viral burden. A proven sensitive and reproducible means of assessing viral load in brain tissue will substantially facilitate clinical (e.g. cross comparison of data between outcome and treatment studies) and basic (e.g. comparison of viral and host message expression within the same RNA sample assessed for viral load) science advances in our understanding of the pathogenesis of neurologic damage associated with AIDS.
