Informatic interrogation of CSF proteomic profiles from HIV-infected subjects implicates acute phase and complement systems in shifting cognitive status.

The prevalence of HIV-Associated Neurocognitive Disorders (HAND) has not changed considerably in the last two decades. Potent antiretroviral therapy (ART) has shifted the severity of HAND to milder phenotypes, but excess morbidity and mortality continue to be associated with HAND. Changes in numerous markers of immune function, inflammation and cellular stress have been repeatedly associated with HAND but the underlying systems that drive these changes have not been identified. In this study we used systems informatics to interrogate the CSF proteomic content of longitudinal samples obtained from HIV-infected adults with stably unimpaired, stably impaired, worsening, or improving neurocognitive (NC) performance. The patterns of change in CSF protein content implicated the induction of acute phase and complement systems as important regulators of NC status. Worsening NC performance was preceded by induction of acute phase and complement systems, while improving NC performance was preceded by a downregulation of these systems.