Despite reduced prevalence of severe forms of HIV-associated
neurocognitive disorders (HAND) on current antiretroviral
therapy (ART) regimens, milder forms of neurocognitive impairment (NCI) remain prevalent in HIV-infected populations. These mild forms of HAND consist of subtypes, probably reflecting distinct, though possibly overlapping, pathophysiological mechanisms. Factors associated with HAND in HIV patients with prolonged viral suppression on ART include older age, low nadir CD4, active HCV
co-infection, and cardiovascular risk factors, but underlying mechanisms and their relationship to innate immune activation, chronic
inflammation, and other features of systemic disease are poorly understood. In this article, we discuss applications and limitations of plasma inflammatory
biomarkers for studies on HAND in HIV patients on ART and describe an analysis pipeline to reduce common sources of noise and increase likelihood of identifying relevant inflammatory
biomarkers. Clinical covariates and comorbidities that influence inflammatory
biomarkers, such as aging,
obesity, metabolic abnormalities, HCV
co-infection, and
substance abuse, are also reviewed. As an example for using this analytic pipeline, we present an exploratory study of 22 plasma inflammatory
biomarkers (IFN-α 2b and -γ, 16
cytokines/
chemokines, sIL-2R,
sCD14, HA, and YKL-40) in a cohort of HIV-infected individuals with advanced disease, frequent HCV
co-infection, and viral suppression on ART. The identification of inflammatory
biomarkers associated with HAND in HIV+ patients on ART may be useful to distinguish between HAND subtypes with distinct pathophysiology, and is important for achieving a systems-level understanding of the biology of these disorders, developing effective
therapies, and evaluating therapeutic outcomes.