The HIV brain amyloid study
Research type
Research Study
Full title
18F]-Florbetaben PET-CT imaging of in vivo β-amyloid deposition in treated HIV-positive patients with cognitive impairment
IRAS ID
208092
Contact name
Jaime Vera
Contact email
Sponsor organisation
Brighton and Sussex University Hospital NHS Trust
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary:
Despite the advent of effective combination antiretroviral (cART) therapy, significant cognitive function impairment has been reported in approximately 15-50% of effectively treated HIV+ individuals within cohorts worldwide . Several pathogenic mechanisms have been implicated in the development of cognitive impairment (CI) in the cART era including persistent neuroinflammation, drug toxicity, life-style factors, and comorbidities. Neurodegeneration has been suggested as one of the pathogenic mechanisms associated with HIV-CI and several reports have described a significant increase in brain β-amyloid deposition in patients with AIDS, however, the presence, and relationship between β-amyloid deposition and cognitive function in HIV+ individuals on cART remains unknown. Until recently it has not been possible to examine in vivo biomarkers of neurodegeneration in HIV+ patients effectively treated with cART. The development of 18F-based radiotracers such as florbetaben to detect β-amyloid plaques, offers the possibility to evaluate in vivo, the degree and distribution of β-amyloid deposition in the brains of HIV+ individuals with cognitive impairment.This study will provide an opportunity to determine if β-amyloid deposition is present in HIV+ individuals with CI, and to study the relationships between β-amyloid deposition, and clinical, and cognitive parameters.Summary of Results:
Imaging with β-amyloid (Aβ) PET has the potential to aid the diagnosis of cognitive impairment affecting people living with HIV (PLWH) when neurodegenerative disorders are considered as part of the differential diagnosis. We evaluated the clinical utility of 18F florbetaben (FBB) PET tracer in PLWH with cognitive symptoms attending a HIV memory clinic Imaging with FBB PET were performed in 20 patients with cognitive complains and concerns about dementia. Neuropsychological testing, plasma neurofilament light protein (NFL), plasma Aβ40 and Aβ42 were obtained during the clinical assessment. CSF Aβ42, tau, and HIV RNA were available for 13 patients that consented to LP. FBB PET images were assessed visually by three readers blinded to the clinical diagnosis, and quantitively by obtaining a composite cortical to cerebellar cortex standardized uptake value ratios (SUVRs). FBB SUVRs from 10 aged matched healthy controls were compared to SUVRs of PLWH. Positive FBB (FBB+) were either visually or quantitatively defined by a composite SUVR >1.3. Cognitive impairment was defined using the Frascati criteria.
Most participants were male (90%) of white ethnicity (90%) with a median age (IQR) of 59 (13) years. Median CD4 count was 651 (314) and CD4/CD8 ratio 0.7 (0.6). All patients were on cART with a plasma HIV RNA< 40 copies/mL. Median (IQR) plasma levels (pg/mL) of NFL, Aβ40 and Aβ42 were 12.1 (5), 263 (111), and 17 (5). Median CSF Aβ40 and tau levels (pg/mL) were 312 (539) and 333 (161). All patients had a CSF RNA <40 copies/mL. 14 patients had objective cognitive impairment including 2 with a clinical diagnosis of suspected dementia. No significant differences in composite SUVRs between PLWH and controls [mean(SD): 1.18(0.03) vs 1.16(0.09); p=0.3]. Four patients were FBB+. Regionally, the greatest SUVRs were observed in the posterior cingulate and superior temporal and frontal superior lobe. Increased composite SUVRs was associated with a reduced Aβ40/Aβ42 ratio (r=-0.4, p<0.41) and protease inhibitor therapy (p< 0.24). No other associations with SUVRs were observed. 18F florbetaben amyloid B PET has potential as an adjunct tool in the management of PLWH with cognitive impairment. Further research is needed to establish its role in the diagnostic algorithm of HAND.REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
16/LO/1611
Date of REC Opinion
25 Oct 2016
REC opinion
Further Information Favourable Opinion