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

BACKGROUND: Protease inhibitor monotherapy (PIM) for 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 assessment and brain MRI 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. Thirty-seven patients randomized to ongoing triple therapy and thirty-nine randomized to PIM were studied. 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 were male (83%) and 64 were 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 the two treatment arms in CBF or regional volumes. Regardless of treatment arm, poorer fine motor performance correlated with lower CBF in the caudate nucleus (p=0.01), thalamus (p=0.04), frontal cortex (p=0.01), occipital cortex (p=0.004) and cingulate cortex (p=0.02), and was associated with smaller supratentorial white matter volume (decrease of 0.16 in Z-score per -1% of total intracranial volume, 95% confidence interval 0.02–0.29, p=0.023). CONCLUSIONS: PIM does not confer additional risk of neurological injury compared with triple therapy. There were correlations between fine motor impairment, grey matter hypoperfusion and white matter volume loss.