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Pharmacokinetics of ethambutol and weight banded dosing in South African adults newly diagnosed with tuberculosis and HIV.
Antimicrob Agents Chemother
December 2024
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Ethambutol is used to treat tuberculosis (TB) in individuals living with HIV. Low concentrations of ethambutol have been reported in patients dosed with the World Health Organization (WHO)-recommended first-line regimen. We analyzed the pharmacokinetics of ethambutol in 61 HIV-positive individuals diagnosed with drug-sensitive TB enrolled in the tuberculosis and highly active antiretroviral therapy (TB-HAART) study.
View Article and Find Full Text PDFDetermining Targets for Antiretroviral Drug Concentrations: A Causal Framework Illustrated With Pediatric Efavirenz Data From the CHAPAS-3 Trial.
Pharmacoepidemiol Drug Saf
December 2024
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Background: Determining a therapeutic window for maintaining antiretroviral drug concentrations within an appropriate range is required for identifying effective dosing regimens. The limits of this window are typically calculated using predictive models. We propose that target concentrations should instead be calculated based on counterfactual probabilities of relevant outcomes and describe a counterfactual framework for this.
View Article and Find Full Text PDFChallenges and Opportunities for Consideration of Efavirenz Drug Repurposing for Alzheimer's Disease Therapeutics.
ACS Pharmacol Transl Sci
October 2024
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, United States.
Therapeutic research and development for Alzheimer's disease (AD) has been an area of intense research to alleviate memory loss and neurodegeneration. There is growing interest in drug repositioning and repurposing strategies for FDA-approved medications as potential candidates that may further advance AD therapeutics. The FDA drug efavirenz has been investigated as a candidate drug for repurposing as an AD medication.
View Article and Find Full Text PDFCausal Inference for Continuous Multiple Time Point Interventions.
Stat Med
December 2024
Division of Biostatistics, Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA.
There are limited options to estimate the treatment effects of variables which are continuous and measured at multiple time points, particularly if the true dose-response curve should be estimated as closely as possible. However, these situations may be of relevance: in pharmacology, one may be interested in how outcomes of people living with-and treated for-HIV, such as viral failure, would vary for time-varying interventions such as different drug concentration trajectories. A challenge for doing causal inference with continuous interventions is that the positivity assumption is typically violated.
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