Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus

Abstract

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting “Biotypes of CNS Complications in People Living with HIV,” held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review

“…Regarding magnetic resonance imaging (MRI), three main approaches are employed: metabolic (magnetic resonance spectroscopy-MRS), structural (MRI volumetrics and diffusion tensor imaging-DTI), and functional (functional MRI-fMRI) [58]. Positron emission tomography (PET) has also been a valuable tool to assess metabolic brain parameters, such as neuroinflammation, neuronal function, microglial activation, and neurotransmitter signaling [59].…”

“…Neuroinflammation and neuronal function during the course of HIV infection can be assessed through glucose metabolism visualization using 18F-fluorodeoxyglucose (FDG) PET [59]. Neuroinflammation is evident in untreated HIV infection by increased uptake of the ligand in the subcortical areas of the brain.…”

Elevated Plasma Protein Carbonyl Concentration Is Associated with More Abnormal White Matter in People with HIV

“…Neuroimaging provides a window into brain health in PWH. With virologic control during ART, the changes seen on macrostructural magnetic resonance imaging (MRI) have become more subtle and localized, especially gray matter volume loss [3]. Increased white matter (WM) abnormalities (e.g., hyperintense regions on T2-weighted images) persist in PWH relative to sociodemographically similar people without HIV, and these progress despite ART [4][5][6][7].…”