Cytomegalovirus encephalitis (CMV-E) is common (20-30%) in patients dying of AIDS, but is rarely diagnosed in life. Since most HIV-infected people are concomitantly infected with CMV, most AIDS patients are at risk of CMV-E. If CMV infection explains some AIDS related neurocognitive impairment, antiviral therapy for CMV could improve cognitive performance. Our autopsy studies indicate that CMV-E is almost always associated with CMV retinitis (CMV-R) and about 42% of CMV-R patients have CMV-E. We have demonstrated more frequent cognitive impairment in CMV-R patients (69%) than in non CMV-R AIDS controls matched for age, education, and CD4 count (37%). Moreover, neuropathological evidence of CMV-E was associated with high rates of neurocognitive impairment before death. The CMV Project will examine specific neurologic, neuropsychologic, and MRI correlates of CMV-R and CMV-E and the subsequent effects of treatment for CMV-R. We will recruit about 139 AIDS patients presenting to our AIDS Occular Research Unit, observe them during l2 weeks of antiviral therapy, and bring to autopsy about 90 patients. We expect CMV-E at autopsy in about 30 patients. In collaboration with the Virology Core we will quantify CMV in CSF and plasma by detection of CMV-DNA after amplification by PCR as a potential diagnostic test for CMV-E and its response to treatment. Postmortem detection of CMV and HIV in brain will be correlated with premortem neurocognitive, neurologic and neuroimaging findings and results of PCR for CMV-DNA in CSF. The project will also explore the relationship between immunogenetic predictors (HLA alleles) in collaboration with the CMV/Immunogenetics project. The findings of this study may a) define the role of CMV-E in cognitive impairment, neurologic symptoms, and neuroimaging abnormalities in AIDS, b) establish the reversibility of these consequences of CMV-E with treatment, c) validate PCR of CSF as a virologic diagnostic method for CMV-E and immunogenetic models as indicators of risk for CMV-E, and d) establish guidelines for virologic and neurocognitive surveillance to provide early identification and treatment for CMV-E.
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