Brain Perfusion, Regional Volumes, and Cognitive Function in Human Immunodeficiency Virus-positive Patients Treated With Protease Inhibitor Monotherapy

Abstract Background Protease inhibitor monotherapy (PIM) for human immunodeficiency virus (HIV) may exert suboptimal viral control in the central nervous system. We determined whether cerebral blood flow (CBF) and regional brain volumes were associated with PIM, and whether specific cognitive domain...

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Published in:Clinical infectious diseases 2019-03, Vol.68 (6), p.1031-1040
Main Authors: Haddow, Lewis J, Godi, Claudia, Sokolska, Magdalena, Cardoso, M Jorge, Oliver, Ruth, Winston, Alan, Stöhr, Wolfgang, Clarke, Amanda, Chen, Fabian, Williams, Ian G, Johnson, Margaret, Paton, Nick, Arenas-Pinto, Alejandro, Golay, Xavier, Jäger, Hans Rolf
Format: Article
Language:English
Subjects:
Adult
Biomarkers
Brain - blood supply
Brain - diagnostic imaging
Brain - pathology
Brain - physiopathology
Cerebrovascular Circulation
Cognition
Female
Functional Neuroimaging
HIV Infections - complications
HIV Infections - drug therapy
HIV Infections - virology
HIV Seropositivity
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Organ Size
Protease Inhibitors - adverse effects
Protease Inhibitors - therapeutic use
Treatment Outcome
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Summary:Abstract Background Protease inhibitor monotherapy (PIM) for human immunodeficiency virus (HIV) may exert suboptimal viral control in the central nervous system. We determined whether cerebral blood flow (CBF) and regional brain volumes were associated with PIM, and whether specific cognitive domains were associated with imaging biomarkers. Methods Cognitive assessments and brain magnetic resonance imaging were performed after the final visit of a randomized HIV-treatment strategy trial. Participants were virologically suppressed on triple therapy at trial entry and followed for 3-5 years. We studied 37 patients randomized to ongoing triple therapy and 39 randomized to PIM. Resting CBF and normalized volumes were calculated for brain regions of interest, and correlated with treatment strategy and neuropsychological performance. Results Mean age was 48.1 years (standard deviation 8.6 years), 63 male (83%), and 64 white (84%). Participants had median 8.1 years (interquartile range 6.4, 10.8) of antiretroviral therapy experience and CD4+ counts of median 640 cells/mm3 (interquartile range 490, 780). We found no difference between treatment arms in CBF or regional volumes. Regardless of treatment arm, poorer fine motor performance correlated with lower CBF in the caudate nucleus (P = .01), thalamus (P = .04), frontal cortex (P = .01), occipital cortex (P = .004), and cingulate cortex (P = .02), and was associated with smaller supratentorial white matter volume (decrease of 0.16 in Z-score per -1% of intracranial volume, 95% confidence interval 0.02-0.29; P = .023). Conclusions PIM does not confer an additional risk of neurological injury compared with triple therapy. There were correlations between fine motor impairment, grey matter hypoperfusion, and white matter volume loss. Clinical Trials Registration ISRCTN-04857074 In virologically-suppressed human immunodeficiency virus-positive patients, protease inhibitor monotherapy did not indicate any additional risks of regional cerebral hypoperfusion or brain volume loss, although some of these neuroimaging biomarkers were associated with impaired fine-motor functions, regardless of regimen.
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/ciy617