Cognitive function in early HIV infection.

This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

Determinants of HIV-induced brain changes in three different periods of the early clinical course: A data mining analysis.

To inform an understanding of brain status in HIV infection, quantitative imaging measurements were derived at structural, microstructural and macromolecular levels in three different periods of early infection and then analyzed simultaneously at each stage using data mining. Support vector machine recursive feature elimination was then used for simultaneous analysis of subject characteristics, clinical and behavioral variables, and immunologic measures in plasma and CSF to rank features associated with the most discriminating brain alterations in each period. The results indicate alterations beginning in initial infection and in all periods studied. The severity of immunosuppression in the initial virus host interaction was the most highly ranked determinant of earliest brain alterations. These results shed light on the initial brain changes induced by a neurotropic virus and their subsequent evolution. The pattern of ongoing alterations occurring during and beyond the period in which virus is suppressed in the systemic circulation supports the brain as a viral reservoir that may preclude eradication in the host. Data mining capabilities that can address high dimensionality and simultaneous analysis of disparate information sources have considerable utility for identifying mechanisms underlying onset of neurological injury and for informing new therapeutic targets.

Brain alterations within the first 100 days of HIV infection.

OBJECTIVE: Brain involvement is a serious complication of HIV infection. The earliest changes in the brain, which represents an anatomic site for viral persistence, are largely unknown. METHODS: This investigation used quantitative Magnetic Resonance methodologies, including high resolution and diffusion tensor (DTI) imaging, to evaluate the brain in 15 HIV and 20 seronegative subjects. All HIV subjects were antibody nonreactive with assay-estimated infection duration of less than 100 days. RESULTS: Brain volumetric analysis revealed reduced parenchyma with enlargement of the third ventricle and brainstem. DTI quantified loss of white matter integrity in the corpus callosum and diffusion alterations in caudate. Cognitive differences were indicated in psychomotor speed and visual recall. There were no differences between antiretroviral-initiated and naïve HIV subgroups. INTERPRETATION: These findings, quantified within 100 days of infection, shed light on the earliest brain changes in HIV infection. Onset of neural injury may date to initial viral invasion and the transient early period of unchecked viremia and marked immunosuppression of the seroconversion period.

Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum.

The purpose of this study was to examine the impact of early suppressive antiretroviral therapy (ART) on brain structure and neurocognitive outcomes. We conducted an observational study of subjects within 1 year of HIV infection. Ten ART-naïve and 10 ART-suppressed individuals were matched for age and infection duration and age-matched to 10 HIV-seronegative controls. Quantitative brain imaging and neurocognitive data were analyzed. Subjects on suppressive ART had diminished corpus callosum structural integrity on macromolecular and microstructural imaging, higher cerebrospinal fluid percent, higher depression scores, and lower functional performance. Early suppressive ART may alter the trajectory of neurological progression of HIV infection, particularly in the corpus callosum.