HIV-Associated Neurocognitive Impairment in the Modern ART Era: Are We Close to Discovering Reliable Biomarkers in the Setting of Virological Suppression?

Alessandra Bandera,Lucia Taramasso,Tricia H Burdo,Andrea Gori,Giorgio Bozzi,Jake A Robinson,Antonio Muscatello

doi:10.3389/fnagi.2019.00187

Abstract

The prevalence of the most severe forms of HIV-associated neurocognitive disorders (HAND) is decreasing due to worldwide availability and high efficacy of antiretroviral treatment (ART). However, several grades of HIV-related cognitive impairment persist with effective ART and remain a clinical concern for people with HIV (PWH). The pathogenesis of these cognitive impairments has yet to be fully understood and probably multifactorial. In PWH with undetectable peripheral HIV-RNA, the presence of viral escapes in cerebrospinal fluid (CSF) might explain a proportion of cases, but not all. Many other mechanisms have been hypothesized to be involved in disease progression, in order to identify possible therapeutic targets. As potential indicators of disease staging and progression, numerous biomarkers have been used to characterize and implicate chronic inflammation in the pathogenesis of neuronal injuries, such as certain phenotypes of activated monocytes/macrophages, in the context of persistent immune activation. Despite none of them being disease-specific, the correlation of several CSF cellular biomarkers to HIV-induced neuronal damage has been investigated. Furthermore, recent studies have been evaluating specific microRNA (miRNA) profiles in the CSF of PWH with neurocognitive impairment (NCI). The aim of the present study is to review the body of evidence on different biomarkers use in research and clinical settings, focusing on PWH on ART with undetectable plasma HIV-RNA.

Highlights

Thirty-seven million people are currently living with HIV infection in the world, according to World Health Organization estimates
LPS levels found to correlate with HIV-associated neurocognitive disorders (HAND) in a subset of HCV-positive participants; LPS found to be a significant predictor of lower processing speed in antiretroviral treatment (ART) suppressed heavy drinkers; BDG levels found to correlate to worse neurocognitive performance
A 2013 work aimed at investigating biomarkers within 98 HIV-infected individuals categorized according to neurocognitive performance, of which 73% of people with HIV (PWH) were on ART and 54% were virally suppressed

Summary

Introduction

Thirty-seven million people are currently living with HIV infection in the world, according to World Health Organization estimates. A certain grade of NCI has been found in PWH on stable antiretroviral treatment (ART) with persistently undetectable viremia, highlighting ongoing brain volume loss and white matter injury without association to HIV viral load (McMurtray et al, 2008; Cardenas et al, 2009; Gongvatana et al, 2009). These data suggest that the direct role of the virus alone cannot explain the presence of HAND and that other factors, such as chronic inflammation, cytokine release and cellular damage, could all be involved in the pathological process. Common autopsy findings in ART-treated PWH included brain endothelial cell activation and alterations in neurochemical synaptic transmission with a lymphocyte infiltrate rather than the monocyte dominant encephalitis observed in advanced pre-ART HIV disease

Objectives

Methods

Results

Conclusion