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

• 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
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciy617

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.