Increased dolutegravir peak concentrations in people living with HIV aged 60 and over and analysis of sleep quality and cognition

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Title: Increased dolutegravir peak concentrations in people living with HIV aged 60 and over and analysis of sleep quality and cognition
Author(s): Elliot, ER
Wang, X
Singh, S
Simmons, B
Vera, JH
Miller, RF
Fitzpatrick, C
Moyle, G
McClure, M
Boffito, M
Item Type: Journal Article
Abstract: Background: Demographic data show an increasingly aging HIV population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older HIV patients. We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50mg once daily in people living with HIV (PLWH) aged 60 and older. Additionally, to address the call for prospective neuropsychiatric toxicodynamic data, we evaluate changes in sleep quality and cognitive function after switching to abacavir (ABC)/lamivudine (3TC)/DTG, over 6 months in this population. Methods: PLWH aged≥60years with HIV-RNA<50copies/mL on any non-DTG based antiretroviral combination were switched to ABC/3TC/DTG. On day 28, 24-hour PK sampling was undertaken. Steady-state PK parameters were compared to a published historical control population aged≤50years. Six validated sleep questionnaires and neurocognitive (Cogstate®) testing were administered pre-switch and over 180 days (NCT02509195). Results: Forty-three participants were enrolled; 40 completed the PK phase. Overall, five discontinued (two due adverse events, both sleep related, 4.6%). DTG maximum concentration (Cmax) was significantly higher in patients≥60 versus controls (GM 4246ng/mL versus 3402ng/mL, p=0.005). In those who completed day 180 (n=38), sleep impairment was higher at day 28 (PSQI median global score 5.0 versus 6.0 p=0.02) but not at day 90 or 180. Insomnia, daytime function, fatigue test scores did not change statistically over time. Conclusion: DTG Cmax was significantly higher in older PLWH. Our data provides clinicians with key information on the safety of prescribing DTG in older PLWH.
Publication Date: 16-May-2018
Date of Acceptance: 1-May-2018
URI: http://hdl.handle.net/10044/1/60661
DOI: https://dx.doi.org/10.1093/cid/ciy426
ISSN: 1058-4838
Publisher: Oxford University Press (OUP)
Journal / Book Title: Clinical Infectious Diseases
Copyright Statement: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Keywords: 06 Biological Sciences
11 Medical And Health Sciences
Microbiology
Publication Status: Published online
Conference Place: United States
Embargo Date: 2019-05-16
Online Publication Date: 2018-05-16
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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