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

• Published in: HIV research & clinical practice Vol. 22; no. 6; pp. 151 - 159
• Main Authors: Mora-Peris, Borja, Keegan, Michael R., Penchala, Sujan Dilly, Vera, Jaime H., Underwood, Jonathan, Khan, Maryam, Herrera, Carolina, Fuchs, Dietmar, Boasso, Adriano, Khoo, Saye, Winston, Alan
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2021; Taylor & Francis Group
• Subjects: Adult; Anti-HIV Agents - therapeutic use; CNS; Cognitive function; CSF; dolutegravir; Emtricitabine; HIV Infections - drug therapy; HIV Integrase Inhibitors - therapeutic use; Humans; integrase inhibitor; Male; MR spectroscopy; raltegravir; Raltegravir Potassium - therapeutic use; CSF; integrase inhibitor; raltegravir; CNS; dolutegravir; Cognitive function; MR spectroscopy
• ISSN: 2578-7489; 2578-7470; 2578-7470
• DOI: 10.1080/25787489.2021.1997880

Background: 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). Methods: 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 (z-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 1 -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. Results: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 z-score difference (95%CI) −0.004 (−0.38/0.37); p = 0.98], PROMs [PHQ-9 median score change: 0 in control arm, −0.5 switch arm (p = 0.57); Beck's depression questionnaire: −1.5 control arm, −1.0 switch arm (p = 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). Conclusions:Switching integrase inhibitor in virologically suppressed PWH without overt neuropsychiatric symptoms resulted in no significant changes in an extensive panel of CNS pharmacodynamics parameters.