Character of CSF inflammation through the course of HIV infection

Abstract

One of the salient features of HIV infection is immune activation and establishment of a chronic inflammatory state. Systemically, this can be detected in activation profiles of T–lymphocytes and elevated levels of inflammatory biomarkers in blood, and is implicated in the pathogenesis of some of the ‘non–AIDS’ morbidity of infection, including cardiovascular disease and some neoplasms. Chronic inflammation is likewise detected in the CNS with elevated levels of inflammatory biomarkers and has been speculated to play a role in HIV–related brain injury. To better define the evolving character of central nervous system (CNS) inflammation accompanying HIV infection and compare it to systemic inflammation, we assessed a panel of 10 soluble inflammatory biomarkers in cerebrospinal fluid (CSF) and blood in grouped subjects representing the spectrum of systemic HIV progression, development of CNS injury and viral suppression. We found that HIV infection was associated with a broad CSF inflammatory response through its full course. Its character diverged from that of systemic inflammation, and changed with systemic disease progression and development of neurological injury. Our findings suggest separate evolution of at least two CNS inflammatory components in those without overt HIV–associated dementia (HAD), one related to lymphocytic inflammation that also associated with CSF pleocytosis and HIV RNA levels and another related to macrophage responses that associated with brain injury. Both of these components were then present in HAD in which CSF inflammation was most prominent and also accompanied by blood–brain barrier disruption, setting this clinical presentation apart as an advanced and marked CNS inflammatory process. Suppression of HIV replication by ART or endogenously in elite controllers was associated with reduced CSF inflammation, though not fully to levels found in HIV uninfected controls. Overall, HIV infection is accompanied by a complex evolving pattern of CNS inflammation that likely relates to interactions of progressive systemic immune and inflammatory reactions, CNS virus populations and CNS injury.