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Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy
- Source :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, Clin Infect Dis
- Publication Year :
- 2021
- Publisher :
- Oxford University Press, 2021.
-
Abstract
- Background Synaptic injury is a pathological hallmark of neurological impairment in people living with human immunodeficiency virus (HIV, PLWH), a common complication despite viral suppression with antiretroviral therapy (ART). Measurement of synaptic density in living humans may allow better understanding of HIV neuropathogenesis and provide a dynamic biomarker for therapeutic studies. We applied novel synaptic vesical protein 2A (SV2A) positron emission tomographic (PET) imaging to investigate synaptic density in the frontostriatalthalamic region in PLWH and HIV-uninfected participants. Methods In this cross-sectional pilot study,13 older male PLWH on ART underwent magnetic resonance imaging (MRI) and PET scanning with the SV2A ligand [11C]UCB-J with partial volume correction and had neurocognitive assessments. SV2A binding potential (BPND) in the frontostriatalthalamic circuit was compared to 13 age-matched HIV-uninfected participants and assessed with respect to neurocognitive performance in PLWH. Results PLWH had 14% lower frontostriatalthalamic SV2A synaptic density compared to HIV-uninfected (PLWH: mean [SD], 3.93 [0.80]; HIV-uninfected: 4.59 [0.43]; P = .02, effect size 1.02). Differences were observed in widespread additional regions in exploratory analyses. Higher frontostriatalthalamic SV2A BPND associated with better grooved pegboard performance, a measure of motor coordination, in PLWH (r = 0.61, P = .03). Conclusions In a pilot study, SV2A PET imaging reveals reduced synaptic density in older male PLWH on ART compared to HIV-uninfected in the frontostriatalthalamic circuit and other cortical areas. Larger studies controlling for factors in addition to age are needed to determine whether differences are attributable to HIV or comorbidities in PLWH. SV2A imaging is a promising biomarker for studies of neuropathogenesis and therapeutic interventions in HIV.<br />Understanding of the biological substrates of neurological impairment in people with human immunodeficiency virus (HIV) is limited. Here, novel in vivo SV2A positron emission tomographic (PET) imaging demonstrated lower synaptic density in older men with virologically suppressed HIV, potentially revealing a new biomarker of neurologic injury.
- Subjects :
- Microbiology (medical)
Oncology
Male
medicine.medical_specialty
brain
Pilot Projects
HIV Infections
Frontostriatal circuit
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
030212 general & internal medicine
SV2A
Aged
NeuroHIV
medicine.diagnostic_test
business.industry
Diagnostic Tests, Routine
HIV
Magnetic resonance imaging
synaptic density
Motor coordination
Major Articles and Commentaries
Infectious Diseases
medicine.anatomical_structure
Cross-Sectional Studies
AcademicSubjects/MED00290
PET
Positron emission tomography
Positron-Emission Tomography
Biomarker (medicine)
Neuropathogenesis
business
Neurocognitive
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15376591 and 10584838
- Volume :
- 73
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
- Accession number :
- edsair.doi.dedup.....108427e224454e6f5dd6629ef92c8e0d