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
Emilie R ElliotMarta Boffito

Abstract

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. 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. 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 ...Continue Reading

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Citations

Nov 18, 2018·Expert Review of Clinical Pharmacology·Giovanni GuaraldiCristina Mussini
Jun 4, 2019·Expert Review of Clinical Pharmacology·Catia Marzolini, Françoise Livio
Jan 8, 2020·AIDS Research and Therapy·Phillip ChanUNKNOWN RV254/SEARCH 010 Research Team
May 30, 2020·British Journal of Clinical Pharmacology·Felix StaderCatia Marzolini
Jul 29, 2020·Journal of Neurovirology·Precious AmusanEsther Fujiwara
Aug 11, 2020·International Journal of STD & AIDS·Ana MilinkovicNneka Nwokolo
Aug 30, 2020·Drugs·Kimberly K ScarsiCourtney V Fletcher
Feb 6, 2020·Journal of the International AIDS Society·David Back, Catia Marzolini
Oct 18, 2019·Therapeutic Advances in Drug Safety·Françoise Livio, Catia Marzolini
Feb 6, 2020·The Journal of Antimicrobial Chemotherapy·Emilie R ElliotAndrew Owen
Jan 5, 2021·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jane A O'HalloranLeah H Rubin
Apr 30, 2021·Expert Opinion on Drug Metabolism & Toxicology·Andrea CalcagnoStefano Bonora
Sep 16, 2021·AIDS Patient Care and STDs·Lucia TaramassoUNKNOWN Behalf of the CISAI Study Group

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