Brain 18F-FDG PET of SIV-infected macaques after treatment interruption or initiation.
J Neuroinflammation
; 15(1): 207, 2018 Jul 14.
Article
en En
| MEDLINE
| ID: mdl-30007411
ABSTRACT
BACKGROUND:
Although rates of severe HIV-associated neurocognitive disorders have declined in the post-antiretroviral treatment (ART) era, subtle deficits persist, possibly exacerbated by treatment non-adherence. The actual effects of ART interruption/initiation on brain glucose metabolism as a reflection of viral replication and neuroinflammation remain unclear. Our study investigates how treatment initiation and interruption alter brain glucose metabolism in SIV-infected macaques, using 18F-FDG PET in correlation with plasma and CSF viral loads (VL) and cytokine levels.METHODS:
SIV-infected macaques (n = 7) underwent ART initiation only, ART interruption only, or both. Five uninfected animals served as controls. 18F-FDG PET imaging was performed at baseline and 1, 3, and 6 months after treatment modification. Mean and maximum standardized uptake values (SUV) for the whole-brain and subregions were calculated. Plasma and CSF VL and cytokine levels were measured. Paired t tests evaluated acute changes in whole-brain SUV from baseline to 1 month, while mixed-effect linear regression models evaluated changes over multiple timepoints and correlated SUV values with disease markers.RESULTS:
ART interruption was associated with increased SUVmean and SUVmax acutely, after 1 month (SUVmean 95% CI [0.044-0.786 g/ml], p = 0.037; SUVmax 95% CI [0.122-3.167 g/ml], p = 0.041). The correlation between SUV and time, however, was not significant when evaluated across all timepoints. Increased SUVmean and SUVmax correlated with decreased CD4+ and CD8+ T-cell counts and increased plasma VL. SUVmax was positively associated with increases in CSF VL, and there were borderline positive associations between SUVmax and IL-2, and between SUVmean and IL-15. The treatment initiation group showed no associations between imaging and disease biomarkers despite viral suppression, reduced cytokine levels, and increased CD4+ and CD8+ T-cell counts.CONCLUSIONS:
ART interruption is associated with increased brain glucose metabolism within 1 month of treatment cessation, which, in concert with increased levels of pro-inflammatory cytokines in the CSF, may reflect neuroinflammation in the setting of viral rebound. Although we cannot assert neurologic damage in association with cerebral hypermetabolism, it is a concerning outcome of ART non-adherence. Treatment initiation, meanwhile, did not result in significant changes in brain metabolism. HIV-induced neuroinflammation may require a longer period to abate than our follow-up period allowed.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Síndrome de Inmunodeficiencia Adquirida del Simio
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Virus de la Inmunodeficiencia de los Simios
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Fluorodesoxiglucosa F18
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Tomografía de Emisión de Positrones
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neuroinflammation
Asunto de la revista:
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos