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Altered neuropsychological performance and reduced brain volumetrics in people living with HIV on integrase strand transfer inhibitors

O’Halloran, Jane A.a; Cooley, Sarah A.b; Strain, Jeremy F.b; Boerwinkle, Annab; Paul, Robertc; Presti, Rachel M.a; Ances, Beau M.b,d

doi: 10.1097/QAD.0000000000002236

Objectives: Neuropsychiatric symptoms have been reported in people living with HIV (PLWH) on integrase strand transfer inhibitors (INSTIs) in postmarketing analysis. Limited data exist regarding brain integrity (function and structure) in PLWH prescribed INSTIs compared with other HIV treatment regimens.

Design: A cross-sectional analysis of PLWH on combined antiretroviral therapy aged more than 18 years at a single institution.

Methods: Neuropsychological tests were administered to calculate domain deficit scores in learning/memory, executive function and motor/psychomotor domains. Cortical and subcortical volumes from MRI were obtained using the FreeSurfer software suite (v5.3).

Results: Of 202 participants, median age 55 (48, 60) years old, 49% were on INSTI-based combined antiretroviral therapy. PLWH on INSTIs were similar to individuals on non-INSTIs in terms of age, sex, race, education years, smoking history, depression scores, psychiatric medication use, presence of hepatitis C infection, history of substance use, HIV infection duration and recent or nadir CD4+ T-cell count. Participants in the INSTI group performed worse than non-INSTI users in the verbal learning and memory domain [1.5 (interquartile range 0, 2.5) versus 1 (0, 2); P = 0.016]. The INSTI and non-INSTI groups were similar for other cognitive domains. Frontal, brain stem and cerebellar volumes were reduced in INSTI compared with non-INSTI users (all P = <0.05).

Conclusion: We demonstrated modest differences in learning/memory performance and smaller brain volumes in PLWH on INSTI-based regimens compared with non-INSTI users. Prospective studies are needed to define mechanisms and the clinical significance of reduced brain integrity in PLWH on INSTIs.

aDivision of Infectious Diseases, Department of Medicine

bDepartment of Neurology, Washington University School of Medicine

cMissouri Institute of Mental Health, University of Missouri St. Louis

dHope Center, Washington University in St. Louis, St. Louis, Missouri, USA.

Correspondence to Jane A. O’Halloran, MB, BCh, BAO, PhD, Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, 4523 Clayton Ave, Campus Box 8051, St. Louis, MO 63110, USA. Tel: +1 314 454 8354; e-mail:

Received 20 January, 2019

Revised 20 March, 2019

Accepted 24 March, 2019

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Copyright © 2019 Wolters Kluwer Health, Inc.