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

Elliot, ER; Wang, X; Singh, S; Simmons, B; Vera, JH; Miller, RF; Fitzpatrick, C; ... Boffito, M; + view all (2019) Increased dolutegravir peak concentrations in people living with HIV aged 60 and over and analysis of sleep quality and cognition. Clinical Infectious Diseases , 68 (1) pp. 87-95. 10.1093/cid/ciy426. Green open access

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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.

Type: Article
Title: Increased dolutegravir peak concentrations in people living with HIV aged 60 and over and analysis of sleep quality and cognition
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/ciy426
Publisher version: http://dx.doi.org/10.1093/cid/ciy426
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10049692
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