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

• The brain was examined in initial stages of HIV using imaging and data mining.
• Brain alterations were identified in all studied periods of the early course.
• Severity of immunosuppression was the highest ranked determinant of onset.
• MMP-1 and CD33+CD36+ monocytes were identified as determinants in every period.
• The brain may represent an early reservoir that precludes viral eradication.

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.