The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid.

T Jordan Walter,Igor Grant,Bin Tang,Scott Letendre,Robert K Heaton,Jared W Young,Donald Franklin,Ronald Ellis,Jennifer Iudicello,William Perry,Arpi Minassian,Debra Rosario Cookson

doi:10.3390/v13071287

Abstract

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = −0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.

Highlights

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health concern
Data were collected from a total of 146 participants, 46 of whom had biomarkers measured in paired plasma and cerebrospinal fluid (CSF) samples collected within an hour, 21 of whom had biomarkers measured only in CSF, and 79 of whom had biomarkers measured only in plasma
In this cross-sectional study of the relationship between HIV, lifetime METH use disorder, and soluble plasma and CSF biomarkers, we found that HIV and METH together were associated with a combination of soluble immune (IL-8, Ccl2), vascular (VEGF), and Because we were interested in the combined effects of HIV and METH, we focused on measures that had evidence of additive or synergistic effects in our correlation analyses

Summary

Introduction

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health concern. One study found that 13% of PWH have a current METH use disorder [1]. Another found that 31% of outpatient PWH used METH in the past year [2]. Even in PWH on anti-retroviral therapy (ART) for one year, the pro-inflammatory cytokine TNFα remains elevated compared to people without HIV [3]. Neuroinflammation can persist in METH users even in sustained abstinence [10]. These changes in the immune system are important as they are associated with—and may be causally related to—negative changes in affect and cognition [11]

Objectives

Methods

Results

Conclusion