Brain structure of perinatally HIV-infected patients on long-term treatment

Abstract

ObjectiveWe aim to give an overview of the available evidence on brain structure and function in PHIV-infected patients (PHIV+) using long-term combination antiretroviral therapy (cART) and how differences change over time.MethodsWe conducted an electronic search using MEDLINE, Embase, and PsycINFO. We used the following selection criteria: cohort and cross-sectional studies that reported on brain imaging differences between PHIV+ of all ages who used cART for at least six months before neuroimaging and HIV-negative controls. Two reviewers independently selected studies, performed data extraction, and assessed quality of studies.ResultsAfter screening 1500 abstracts and 343 full-text articles, we identified 19 eligible articles. All included studies had a cross-sectional design and used MRI with different modalities: structural MRI (n = 7), diffusion tensor imaging (DTI) (n = 6), magnetic resonance spectroscopy (n = 5), arterial spin labeling (n = 1), and resting-state functional neuroimaging (n = 1). Studies showed considerable methodological limitations and heterogeneity, preventing us to perform meta-analyses. DTI data on white matter microstructure suggested poorer directional diffusion in cART-treated PHIV+ compared with controls. Other modalities were inconclusive.ConclusionEvidence may suggest brain structure and function differences in the population of PHIV+ on long-term cART compared with the HIV-negative population. Because of a small study population, and considerable heterogeneity and methodological limitations, the extent of brain structure and function differences on neuroimaging between groups remains unknown.

Brain Magnetic Resonance Imaging Findings Associated With Cognitive Impairment in Children and Adolescents With Human Immunodeficiency Virus in Zambia

“…Previous volumetric neuroimaging studies of pediatric patients with HIV show varied results. 3,7,8,12 Smaller cerebral brain volumes in HIV-infected youth have been described in three recent studies, including a Dutch cohort of patients aged eight to 18 years, 34 a South African cohort aged nine to 11 years, 8 and a Chinese cohort aged 11 to 17 years. 35 Decreased regional cortical surface areas were FIGURE 1.…”

“…5 Some hypotheses include viral compartmentalization in the central nervous system, persistent neuroinflammation despite viral suppression, neurotoxicity of commonly used antiretroviral drugs, vascular injury, and socioeconomic or environmental factors. 4,5,[7][8][9][10][11] Neuroimaging biomarkers of HIV-associated cognitive impairment are appealing because of their noninvasive nature and the ability to identify abnormalities that may contribute to cognitive impairment, such as brain injury, opportunistic infections, and cerebrovascular disease. 3 Current literature describing brain abnormalities in perinatally infected children and adolescents with HIV suggest differences in global and regional brain volumes and white matter structural integrity.…”

“…Frequently reported findings include decreased gray and white matter volumes, white matter hyperintensities, and diffusion tensor imaging abnormalities. 3,7,[12][13][14][15] Regional differences in brain volumes have been identified in the frontal and temporal lobes and basal ganglia, although findings have been inconsistent across studies. 7,8,12 Evidence of increased risk of cerebrovascular disease in children with HIV infection is also documented, with vasculopathy, opportunistic vasculitis, cardioembolism, and coagulopathy associated with HIV infection.…”

“…3,7,[12][13][14][15] Regional differences in brain volumes have been identified in the frontal and temporal lobes and basal ganglia, although findings have been inconsistent across studies. 7,8,12 Evidence of increased risk of cerebrovascular disease in children with HIV infection is also documented, with vasculopathy, opportunistic vasculitis, cardioembolism, and coagulopathy associated with HIV infection. 16 Magnetic resonance imaging (MRI) characteristics associated with cognitive outcomes in children and adolescents with HIV are more limited, although one study of HIV-infected adolescents in South Africa identified an association between global intelligence (intelligence quotient) and total gray and white matter volumes.…”

“…8 However, prior studies have been somewhat limited by inclusion of a mix of ART-treated and ART-naive subjects, lack of information on clinical characteristics of the studied population, and lack of an appropriate control group. 7,8 The present study aims to address some of the limitations of prior investigations and to describe neuroimaging characteristics associated with cognitive function in Zambian children and adolescents living with HIV. Zambia is an ideal location to study chronic complications of HIV because of the relatively high prevalence of HIV infection and widespread use of ART.…”