PET in HIV Study
Research type
Research Study
Full title
PET imaging individuals living with HIV: a [11C] PBR28 PET-CT study
IRAS ID
193628
Contact name
Alan Winston
Contact email
Duration of Study in the UK
0 years, 9 months, 1 days
Research summary
Research Summary
This study plans to investigate if there is a relationship between detailed brain tests and the level of the HIV latent reservoir (these are areas were HIV can lie hidden, sleeping within cells in places such as the brain, gut and lymphatic system). We will use a brain scan called PET-CT (Positron Emission Tomography-Computed Tomography) to detect subtle changes not usually picked up by routine MRI scans. We will see how this relates to measures of the HIV reservoir in blood.
Summary of Results
Background:
Despite antiretroviral therapy (ART), persistent immune activation is described in people-with-HIV (PWH), possibly related to the latent HIV reservoir.
Using translocator protein (TSPO) PET brain imaging, neuroinflammation has been reported in PWH on ART. Early ART initiation is associated with reduced markers of inflammation.
We hypothesised that neuroinflammation, measured using TSPO [11C]PBR28, would be lower in PWH who initiated ART during acute (aPWH) versus chronic HIV infection (cPWH).
Consensus on the optimal reference region in TSPO studies has not been established, hence we investigated [11C]PBR28 binding in PWH normalised to reference regions previously used in TSPO studies.Method:
Twenty TSPO high-affinity binders, neurologically asymptomatic PWH on virologically suppressive ART (9 aPWH, 11 cPWH) and 15 control participants underwent [11C]PBR28 PET scanning.
Using a two-tissue compartmental model, distribution volume ratios (DVR) were calculated using the reference regions: cortical grey matter, total grey matter, cerebellum, cerebellar grey matter and cerebral white matter, at 20 pre-defined regions of interest (ROIs).
Differences in DVRs were compared between the groups using Kruskall-Wallis and Mann-Whitney U-tests.Result:
All PWH were male with median age 40 and 45 years in the aPWH and cPWH, respectively, while 4/15 control participants were female and median age was 26 years.
Median duration between HIV diagnosis and ART initiation was 3.6 and 16.0 weeks in aPWH and cPWH, respectively. Significant differences (p<0.05) in DVRs were observed between cPWH and control participants and between cPWH and aPWH in certain ROIs.
No differences in DVRs at any ROIs were noted between aPWH and controls.
When utilising the cerebellum and cerebellar grey matter as reference regions, the greatest differences in DVR between the groups were observed.Conclusions:
Significant differences in [11C]PBR28 binding were identified between cPWH and control participants; [11C]PBR28 binding differences between aPWH versus cPWH were observed less frequently.
Neuroinflammation in aPWH and control participants were similar, suggesting that early ART initiation may mitigate persistent neuroinflammatory responses.
Cerebral [11C]PBR28 DVR binding in PWH is dependent on the reference region and urgent consensus is required on the optimal reference region in TSPO studies in PWH.REC name
London - Camden & Kings Cross Research Ethics Committee
REC reference
16/LO/0096
Date of REC Opinion
3 Mar 2016
REC opinion
Further Information Favourable Opinion