Brain perfusion, regional volumes and cognitive function in HIV positive patients treated with protease inhibitor monotherapy

Lewis J. Haddow, Claudia Godi, Magdalena Sokolska, Manuel Jorge Cardoso, Ruth Oliver, Alan Winston, Wolfgang Stöhr, Amanda Clarke, Fabian Chen, Ian G. Williams, Margaret Johnson, Nick Paton, Alejandro Arenas-Pinto, Xavier Golay, Hans Rolf Jäger

Research output: Contribution to journalArticle

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/mm 3 (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

Original languageEnglish
Pages (from-to)1031-1040
Number of pages10
JournalClinical Infectious Diseases
Volume68
Issue number6
Early online date31 Jul 2018
DOIs
Publication statusPublished - 5 Mar 2019

Keywords

  • HIV
  • magnetic resonance imaging
  • cerebral blood flow
  • cognitive function
  • white matter

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