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BackgroundIn the absence of significant opportunistic infection, the most common alterations on neuroimaging in the brains of patients with AIDS include enlarged cerebrospinal fluid spaces, white-matter loss, volume loss in striatal structures, and white-matter signal abnormalities. Although previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them.ObjectiveTo examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV) encephalitis and neurodegeneration.DesignMorphometric analysis of magnetic resonance imaging in seropositive cases with matched seronegative controls, and the correlation of these volumes to neuropathological measures in autopsied seropositive cases.SettingUniversity of California, San Diego, HIV Neurobehavioral Research Center.SubjectsTwenty-one seropositive subjects studied at autopsy and 19 seronegative cases.Main outcome measuresIn vivo structural magnetic resonance imaging data analyzed by quantitative methods, with comparison of volumes from magnetic resonance imaging and neuropathological data from autopsies.ResultsThe HIV-seropositive subjects demonstrated cerebrospinal fluid increases relative to seronegative controls. These increases were associated with a significant decrease in the volumes of cerebral and cerebellar white matter, caudate nucleus, hippocampus, and, to a lesser extent, cerebral cortex. The volume of cerebral white-matter tissue with elevated signal was also increased. This signal elevation in white matter predicted the autopsy diagnosis of HIV encephalitis, as well as the extent of dendritic loss as assessed by analysis of microtubule-associated protein 2 immunoreactivity.ConclusionsWhite-matter and cortical damage resulting from HIV disease are closely related. In vivo magnetic resonance imaging may be a valuable adjunct in the assessment of patients at risk for developing HIV encephalitis.

Background: Neuropsychological (NP) impairment is a relatively common sequela in human immunodeficiency virus (HIV)–infected individuals with advanced disease. Early antecedents of NP dysfunction, however, remain poorly understood. Objective: To determine whether early markers of immunocompetence and viral replication in individuals who have undergone seroconversion would be of prognostic value in identifying subjects who would become cognitively impaired. Methods: Seventy-four subjects with estimable seroconversion dates and normal cognition at baseline (a median of 1 year after seroconversion) received NP and laboratory evaluations, including reverse transcription–polymerase chain reaction measurements of plasma (N = 74) and cerebrospinal fluid (n = 47) levels of HIV RNA. Subjects were followed up longitudinally, and were considered to have reached the end point if they became cognitively impaired. Results: Using Kaplan-Meier estimates, the subgroups with the most rapid progression to NP impairment were (1) subjects with early reductions in CD4 counts (<400 cells/µL at baseline; P = .007) and (2) those with elevated plasma HIV RNA values (>4.5 log[sub 10] copies/mL; P = .03) early after seroconversion. Using proportional hazards modeling, the highest-risk subjects had both CD4 counts less than 400 cells/µL and HIV RNA levels greater than 4.5 log[sub 10] copies/mL (risk ratio, 6.0; P = .01). In most subjects (7/9 [78%]), NP impairment developed before an acquired immunodeficiency syndrome–defining illness. Conclusions: Neurocognitive outcomes in HIV are strongly influenced by very early systemic virological and immunological events. Patients with high plasma levels of HIV RNA and low CD4 counts early after infection should be aggressively treated to prevent immunological decline and NP deterioration. [ABSTRACT FROM AUTHOR]