Antiretroviral drug concentrations in brain tissue of adult decedents.

AIDS
Micol FerraraScott L Letendre

Abstract

Determine concentrations of antiretroviral therapy (ART) drugs in the human brain. Cohort study of persons with HIV who consented to antemortem assessment and postmortem autopsy. Eleven persons with HIV who were taking ART at the time of death and had detectable concentrations of at least one ART drug in intracardiac aspirate at autopsy were evaluated. Autopsies were performed within 24 h of death and brain tissue was stored at -80 °C. Concentrations of 11 ART drugs were measured in three brain regions (globus pallidus, cortical gray matter, white matter) by HPLC tandem mass spectrometry with a lower limit of quantification of 25 ng/ml. Participants were mostly men (82%) with a mean age of 40.4 years. Drug concentrations in brain tissue were highly variable and exceeded published concentrations in cerebrospinal fluid for several drugs, including for tenofovir, efavirenz, and lopinavir. Drug concentrations correlated most strongly between cortical gray matter and globus pallidus (rho = 0.70) but less well between globus pallidus and white matter (rho = 0.43). Combining all drugs and brain regions (n = 89), higher drug concentrations in brain were associated with longer estimated duration of HIV infection (P = 0.015), lower HIV R...Continue Reading

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Citations

Feb 2, 2021·Neuroscience Letters·Melanie R Nicol, MaryPeace McRae
Apr 2, 2021·Reviews in Medical Virology·Sonia Romero-CorderoConstanza Morén
Apr 30, 2021·Expert Opinion on Drug Metabolism & Toxicology·Andrea CalcagnoStefano Bonora
Aug 26, 2021·Retrovirology·E A Nickoloff-BybelP J Gaskill
Sep 12, 2021·The Journal of Antimicrobial Chemotherapy·Thibaut GeléAurélie Barrail-Tran

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