Increased Dolutegravir Peak Concentrations in People Living With Human Immunodeficiency Virus Aged 60 and Over, and Analysis of Sleep Quality and Cognition.

Elliot, Emilie R ORCID: 0000-0001-7736-9883, Wang, Xinzhu, Singh, Suveer, Simmons, Bryony ORCID: 0000-0002-3207-9935, Vera, Jaime H ORCID: 0000-0002-1165-0573, Miller, Robert F ORCID: 0000-0003-2067-4291, Fitzpatrick, Colin ORCID: 0000-0001-5764-5860, Moyle, Graeme, McClure, Myra and Boffito, Marta ORCID: 0000-0002-2213-1103 (2019) Increased Dolutegravir Peak Concentrations in People Living With Human Immunodeficiency Virus Aged 60 and Over, and Analysis of Sleep Quality and Cognition. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 68 (1). pp. 87-95.

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Official URL: http://dx.doi.org/10.1093/cid/ciy426

Abstract

<h4>Background</h4>Demographic data show an increasingly aging human immunodeficiency virus (HIV) population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older people living with HIV (PLWH). We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50 mg once daily in PLWH aged 60 and older. Additionally, to address calls for prospective neuropsychiatric toxicodynamic data, we evaluated changes in sleep quality and cognitive functioning in this population after switching to abacavir (ABC)/lamivudine (3TC)/DTG over 6 months.<h4>Methods</h4>PLWH ≥60 years with HIV-viral load <50 copies/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 ≤50 years. We administered 6 validated sleep questionnaires and neurocognitive (Cogstate) testing pre-switch and over 180 days.<h4>Results</h4>In total, 43 participants enrolled, and 40 completed the PK phase. Overall, 5 discontinued (2 due to sleep-related adverse events, 4.6%). DTG maximum concentration (Cmax) was significantly higher in patients ≥60 years old versus controls (geometric mean 4246 ng/mL versus 3402 ng/mL, P = .005). In those who completed day 180 (n = 38), sleep impairment (Pittsburgh Sleep Quality Index) was marginally higher at day 28 (P = .02), but not at days 90 or 180. Insomnia, daytime functioning, and fatigue test scores did not change statistically over time.<h4>Conclusions</h4>DTG Cmax was significantly higher in older PLWH. Our data provides clinicians with key information on the safety of prescribing DTG in older PLWH.

Item Type:	Article
Uncontrolled Keywords:	Humans, HIV Infections, Oxazines, Piperazines, Pyridones, Heterocyclic Compounds, 3-Ring, HIV Integrase Inhibitors, Prospective Studies, Cognition Disorders, Aged, Aged, 80 and over, Middle Aged, Female, Male, Drug-Related Side Effects and Adverse Reactions, Sleep Wake Disorders
Depositing User:	Symplectic Admin
Date Deposited:	04 Mar 2020 16:08
Last Modified:	19 Jan 2023 00:00
DOI:	10.1093/cid/ciy426
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3076609