Date of Award

January 2022

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)



First Advisor

Serena Spudich


Background: Synaptic injury is a pathological hallmark of neurological impairment in people living with HIV (PLWH), a common complication despite viral suppression with antiretroviral therapy (ART). However, there are no biomarkers sensitive to neurocognitive impairment in PLWH. 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 (HIV-) participants.

Methods: In this cross-sectional pilot study,13 older male PLWH on ART underwent neurocognitive assessments, MRI, and PET scanning with the SV2A ligand [11C]UCB-J with partial volume correction. SV2A binding potential (BPND) in the frontostriatalthalamic circuit was compared to 13 age-matched HIV- participants, and assessed with respect to neurocognitive performance in PLWH.

Results: PLWH had 14% lower frontostriatalthalamic SV2A synaptic density compared to HIV- (PLWH: mean [SD], 3.93 [0.80]; HIV-: 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 this pilot study, SV2A PET imaging revealed reduced synaptic density in older male PLWH on ART compared to HIV- both regionally in the frontostriatalthalamic circuit and more globally. 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.


This is an Open Access Thesis.

Open Access

This Article is Open Access