Cerebral function parameters in people with HIV switching integrase inhibitors: a randomized controlled trial

Mora-Peris, Borja, Keegan, Michael R, Penchala, Sujan Dilly, Vera, Jaime H, Underwood, Jonathan, Khan, Maryam, Herrera, Carolina, Fuchs, Dietmar, Boasso, Adriano, Khoo, Saye ORCID: 0000-0002-2769-0967
et al (show 1 more authors) (2021) Cerebral function parameters in people with HIV switching integrase inhibitors: a randomized controlled trial. HIV RESEARCH & CLINICAL PRACTICE, 22 (6). pp. 151-159.

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<b>Background:</b> Different antiretroviral therapies (ARTs) may have differing effects on central nervous system (CNS) function. We assessed CNS pharmacodynamic effects of switching integrase inhibitors in people-with-HIV (PWH).<b>Methods:</b> PWH on tenofovir-DF/emtricitabine plus raltegravir 400 mg twice daily with suppressed plasma HIV RNA and without overt neuropsychiatric symptoms were randomly allocated on a 1:2 basis to remain on raltegravir or switch to dolutegravir 50 mg once daily for 120 days. Pharmacodynamic parameters assessed included cognitive function (<i>z</i>-score of 7 domains), patient-reported outcome measures (PROMs; PHQ-9 and Beck's depression questionnaires), cerebral metabolite ratios measured by proton magnetic resonance spectroscopy (H<sup>1</sup>-MRS) and plasma and cerebrospinal fluid (CSF) HIV RNA. Pharmacokinetic parameters were also assessed in plasma and CSF. Changes and factors associated with changes in pharmacodynamics parameters were assessed.<b>Results:</b>In 20 subjects (19 male, 14 white ethnicity, median age 43 years (IQR: 11.5) and CD4 + count 717 (SD: 298) cells/µL), over 120 days there were no statistically significant changes in cognitive function [mean <i>z</i>-score difference (95%CI) -0.004 (-0.38/0.37); <i>p</i> = 0.98], PROMs [PHQ-9 median score change: 0 in control arm, -0.5 switch arm (<i>p</i> = 0.57); Beck's depression questionnaire: -1.5 control arm, -1.0 switch arm (<i>p</i> = 0.38)], nor cerebral metabolite ratios between study arms. CSF HIV RNA was <5 copies/mL at baseline and day 120 in all subjects. Geometric mean pre-dose CSF dolutegravir concentration was 7.6 ng/mL (95% CI: 5.2-11.1).<b>Conclusions:</b>Switching integrase inhibitor in virologically suppressed PWH without overt neuropsychiatric symptoms resulted in no significant changes in an extensive panel of CNS pharmacodynamics parameters.

Item Type: Article
Uncontrolled Keywords: Cognitive function, integrase inhibitor, raltegravir, dolutegravir, CNS, MR spectroscopy, CSF
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 26 Nov 2021 08:35
Last Modified: 18 Jan 2023 21:24
DOI: 10.1080/25787489.2021.1997880
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3143850