Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy.
Clin Infect Dis
; 73(8): 1404-1411, 2021 10 20.
Article
en En
| MEDLINE
| ID: mdl-34050746
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]; Pâ =â .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 (râ =â 0.61, Pâ =â .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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
Tomografía de Emisión de Positrones
Tipo de estudio:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Límite:
Aged
/
Humans
/
Male
Idioma:
En
Año:
2021
Tipo del documento:
Article