RESUMEN
Poor antiretroviral penetration may contribute to human immunodeficiency virus (HIV) persistence within the brain and to neurocognitive deficits in opiate abusers. To investigate this problem, HIV-1 Tat protein and morphine effects on blood-brain barrier (BBB) permeability and drug brain penetration were explored using a conditional HIV-1 Tat transgenic mouse model. Tat and morphine effects on the leakage of fluorescently labeled dextrans (10-, 40-, and 70-kDa) into the brain were assessed. To evaluate effects on antiretroviral brain penetration, Tat+ and Tat- mice received three antiretroviral drugs (dolutegravir, abacavir, and lamivudine) with or without concurrent morphine exposure. Antiretroviral and morphine brain and plasma concentrations were determined by LC-MS/MS. Morphine exposure, and, to a lesser extent, Tat, significantly increased tracer leakage from the vasculature into the brain. Despite enhanced BBB breakdown evidenced by increased tracer leakiness, morphine exposure led to significantly lower abacavir concentrations within the striatum and significantly less dolutegravir within the hippocampus and striatum (normalized to plasma). P-glycoprotein, an efflux transporter for which these drugs are substrates, expression and function were significantly increased in the brains of morphine-exposed mice compared to mice not exposed to morphine. These findings were consistent with lower antiretroviral concentrations in brain tissues examined. Lamivudine concentrations were unaffected by Tat or morphine exposure. Collectively, our investigations indicate that Tat and morphine differentially alter BBB integrity. Morphine decreased brain concentrations of specific antiretroviral drugs, perhaps via increased expression of the drug efflux transporter, P-glycoprotein.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Barrera Hematoencefálica/efectos de los fármacos , VIH-1/genética , Morfina/efectos adversos , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/virología , Permeabilidad Capilar , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/virología , Dextranos/farmacocinética , Didesoxinucleósidos/farmacocinética , Femenino , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacocinética , Infecciones por VIH/metabolismo , Infecciones por VIH/psicología , Infecciones por VIH/virología , VIH-1/metabolismo , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/virología , Lamivudine/farmacocinética , Ratones , Ratones Transgénicos , Modelos Biológicos , Trastornos Neurocognitivos/metabolismo , Trastornos Neurocognitivos/psicología , Trastornos Neurocognitivos/virología , Oxazinas , Piperazinas , Piridonas , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
A higher proportion of people in correctional settings have, or are at risk for, hepatitis C virus (HCV) due to socioeconomic factors, mental health concerns, substance use disorders, history of high-risk experiences, and more. Compared with the general population, the prevalence of HCV is 10 times higher among people who are incarcerated. The objective of this retrospective cohort study was to describe the HCV treatment cascade in a pharmacist-led clinic model, from referral through treatment completion and documentation of cure. Pharmacists in the Virginia Department of Corrections, in collaboration with Virginia Commonwealth University, established and led a telemedicine HCV clinic. A total of 1,040 incarcerated individuals with chronic HCV infection were treated between January 2020 and January 2022. In this study, the clinical endpoint was the number of patients achieving a 12-week sustained virological response (SVR12), which is considered cure of an HCV infection. The economic endpoint was total dollars spent per patient to achieve the SVR12. Participants were HCV treatment naïve, positive for HCV genotypes 1-6, not concurrently infected with HIV, and without decompensated liver disease. The overall cure rate was 97% with no discontinuation due to adverse effects. The cost-to-cure ratio was $23,223/person achieving SVR12.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Humanos , Hepacivirus , Antivirales/uso terapéutico , Farmacéuticos , Estudios Retrospectivos , Virginia/epidemiología , Resultado del Tratamiento , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , GenotipoRESUMEN
The purpose of this report is to: 1) Identify linkages across the EPA statements, Center for the Advancement of Pharmacy Education 2013 Educational Outcomes (CAPE 2013) and the Joint Commission of Pharmacy Practitioners' Pharmacist Patient Care Process (PPCP); 2) Provide ways EPA statements can be used to communicate core skills that are part of the entry-level pharmacist identity; 3) Suggest a potential roadmap for AACP members on how to implement EPA statements.