HIV DNA and neurocognitive impairment in older subjects on suppressive ART.

Type: Poster
Title: HIV DNA and neurocognitive impairment in older subjects on suppressive ART.
Authors: Oliveira M, Murrell B, Perez-Santiago J, Vargas M, Ellis R, Letendre S, Grant I, Smith D, Woods S, Gianella S
Year: 2015
Publication: Conference on Retroviruses and Opportunistic Infections

Background: Older adults are at high risk for HIV-associated neurocognitive impairment (NCI), but the underlying neurobiological mechanisms of this heightened risk are poorly understood.

Methods: This study included 18 younger (22-40 years) and 26 older (50-71 years) chronically HIV+ subjects on suppressive ART. Subjects were characterized for NC functioning by Global Deficit Score (GDS) using a standardized battery consistent with Frascati recommendations for neuroAIDS. Levels of HIV DNA were measured in PBMC by droplet digital PCR, soluble markers of monocyte and general immune activation (sCD14, sCD163, MCP-1, IL-6, IL-8, TNF-α, IP-10 and Neopterin) were measured in blood and cerebrospinal fluid (CSF) by immunoassay. Associations between GDS and other variables were evaluated by regression analysis adjusted for estimated duration of infection (EDI) and age. Mann Whitney tests were used to detect differences between groups.

Results: Sixteen (36.4%) subjects had NCI (GDS ≥0.5). GDS was not associated with current or nadir CD4 in either age group (p>0.5). Stepwise regression with AIC model selection starting with a model containing all identified predictors of GDS retained only age group (young vs old) and HIV DNA, with a significant interaction between age group and HIV DNA (p=0.022). In the younger group, no association was found between GDS and HIV DNA levels (ρ=-0.08, p>0.5). For older subjects, higher levels of HIV DNA were associated with GDS (ρ=0.57, p=0.003), which remained significant after adjusting for EDI and age. Higher HIV DNA levels were specifically associated with deficits in executive functions among older individuals (p= 0.004), while no differences were found for other abilities in either age group. Higher levels of IL-8 in blood plasma were associated with worse GDS among older subjects after adjusting for age (p=0.04), but not for the younger subjects. No associations were found between GDS and the other markers.

Conclusions: Prior studies have linked the HIV DNA reservoir size to NCI and our findings identify that this association is strongest in HIV+ adults older than 50, along with IL-8, which we have previously linked to evidence of inflammation on brain magnetic resonance spectroscopy. These findings add to emerging evidence that the correlates of NCI differ in older and younger HIV+ adults, which supports tailoring therapy based on age. In addition, our findings suggest that interventions aiming to reduce the HIV DNA reservoir may impact the central nervous system.