Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe
Date
2021-05-24
Journal Title
Journal ISSN
Volume Title
Publisher
BMC
Abstract
Background: Drug potency is a pharmacological parameter defining dose or concentration of drug required to
obtain 50% of the drug’s maximal effect. Pharmacokinetic-pharmacodynamic modelling and simulation allows
estimation of potency and evaluate strategies improving treatment outcome. The objective of our study is to
determine potency of atazanavir in hair, defined as atazanavir level in hair associated with 50% probability of failing
to achieve viral load below 1000 copies/ml among adolescents, and explore the effect of participant specific
variables on potency.
Methods: A secondary analysis was performed on data from a previous study conducted in HIV-infected
adolescents failing 2nd line ART from Harare central hospital, Zimbabwe, between 2015 and 2016. We simulated
atazanavir concentrations in hair using NONMEM (version 7.3) ADVAN 13, based on a previously established
pharmacokinetic model. Logistic regression methods were used for PKPD analysis. Simulations utilising PKPD model
focused on estimation of potency and exploring the effect of covariates.
Results: The potency of atazanavir in hair was found to be 4.5 ng/mg hair before adjusting for covariate effects.
Participants at three months follow-up, reporting adequate adherence, having normal BMI-for-age, and cared for by
mature guardians had increased potency of atazanavir in hair of 2.6 ng/mg, however the follow-up event was the
only statistically significant factor at 5% level.
Conclusion: Atazanavir in hair in the range 2.6 to 4.5 ng/mg is associated with above 50% probability of early viral
load suppression. Adherence monitoring to adolescents with lower potency of atazanavir is recommended. The
effect self-reported adherence level, BMI-for-age, and caregiver status require further evaluation.
Description
CITATION: Ngara, B., et al. 2021. Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe. BMC Pharmacology and Toxicology, 22:29, doi:10.1186/s40360-021-00497-8.
The original publication is available at https://bmcpharmacoltoxicol.biomedcentral.com
The original publication is available at https://bmcpharmacoltoxicol.biomedcentral.com
Keywords
Pharmacodynamics, Atazanavir, Pharmacokinetics, Antiretroviral drugs -- Zimbabwe, Adolescents, Hair -- Analysis
Citation
Ngara, B., et al. 2021. Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe. BMC Pharmacology and Toxicology, 22:29, doi:10.1186/s40360-021-00497-8