Cytokines, Hepatic Fibrosis, and Antiretroviral Therapy Role in Neurocognitive Disorders HIV Related

The HIV may trigger a process of neuronal loss and axonal degeneration throughout the brain, which is carried on by the immune system releasing of proinflammatory cytokines, so that chronic inflammation associated with dysregulated innate immune response, glial cell dysfunction, and adverse antiretroviral therapy (ART) effect play an important role causing milder HIV-associated neurocognitive disorders or asymptomatic neurocognitive impairment. All patients have been tested for neurocognitive functioning through a comprehensive, five-domain neuropsychological battery performed in the study. Human cytokine (interleukin [IL]-6, IL-8, IL-18, and tumor necrosis factor [TNF]-) and brain-derived neurotrophic factor serum levels were quantified using ELISAs, and the hepatic fibrosis was estimated using the noninvasive Fibrosis 4 (FIB-4) score. The study showed a group of 40 HIV-infected individuals and it was observed that almost 40% of HIV+ individuals, even if clinically asymptomatic, displayed some degree of neurocognitive dysfunction, compared to normative performance standards, at least in two cognitive areas. The functions affected the most were memory, attention, executive function, and psychomotor processing speed. Three cytokines (IL-6, IL-8, and IL-18) to be significantly linked to test results in specific neurocognitive domain were found. Treatments with nucleoside reverse transcriptase inhibitor plus non-nucleoside reverse transcriptase inhibitor alone were instead associated with poor neurocognitive outcome, especially in verbal fluency, fine motility, and Zung Depression Scale. Elevated value of FIB-4 score showed an opposite connection with cognitive performance as well, underlining the direct association between hepatic steatosis and neurocognitive deficit. The cytokine panel and the FIB-4 score can predict presence or worsening of neurocognitive functions in HIV-infected individuals. An ART switch can be suggested according to the neurocognitive domain involved the most, advising a therapy with protease inhibitors or/and integrase inhibitors to improve fluency, executive functions, and to prevent depression.