A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir: a study of HIV-infected Zimbabwean adolescents

Bernard Ngara,Charles Fungai Brian Nhachi,Simbarashe Rusakaniko,Babill Stray-Pedersen,Tariro Dianah Chawana,Simbarashe Zvada

doi:10.1186/s40360-020-00437-y

Bernard Ngara, Charles Fungai Brian Nhachi + Show 4 more

Open Access

https://doi.org/10.1186/s40360-020-00437-y

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Abstract

BackgroundAdolescents experience higher levels of non-adherence to HIV treatment. Drug concentration in hair promises to be reliable for assessing exposure to antiretroviral (ARV) drugs. Pharmacokinetic modelling can explore utility of drug in hair. We aimed at developing and validating a pharmacokinetic model based on atazanavir/ritonavir (ATV/r) in hair and identify factors associated with variabilities in hair accumulation.MethodsWe based the study on secondary data analysis whereby data from a previous study on Zimbabwean adolescents which collected hair samples at enrolment and 3 months follow-up was used in model development. We performed model development in NONMEM (version 7.3) ADVAN 13.ResultsThere is 16% / 18% of the respective ATV/r in hair as a ratio of steady-state trough plasma concentrations. At follow-up, we estimated an increase of 30% /42% of respective ATV/r in hair. We associated a unit increase in adherence score with 2% increase in hair concentration both ATV/r. Thinner participants had 54% higher while overweight had 21% lower atazanavir in hair compared to normal weight participants. Adolescents receiving care from fellow siblings had atazanavir in hair at least 54% less compared to other forms of care.ConclusionThe determinants of increased ATV/r concentrations in hair found in our analysis are monitoring at follow up event, body mass index, and caregiver status. Measuring drug concentration in hair is feasibly accomplished and could be more accurate for monitoring ARV drugs exposure.

Highlights

Adolescents experience higher levels of non-adherence to Human Immunodeficiency Virus (HIV) treatment
We describe the rate of change of amount of drug between compartments in Fig. 1 using the differential equations: Fig. 1 Schematic representation of the structural population PK model used to predict atazanavir and ritonavir concentrations measured in hair
Ten percent of the study participants were under the care of fellow siblings below the age of 19 years while others were under the care of parents or relatives

Summary

Introduction

Drug concentration in hair promises to be reliable for assessing exposure to antiretroviral (ARV) drugs. Zimbabwe has a prevalence of 13.3%, with 1.3 million people living with HIV including 77,000 children and adolescents [2]. The methods used for assessing adherence and exposure to ARV drugs include selfreported missed doses, monitoring pharmacy refills and conducting pill counts, use of electronic monitoring devices, measuring ARV concentration in plasma or hair [12,13,14]. Quantifying ARV drugs in hair provides information of both steady-state pharmacokinetics and long term adherence and has shown to predict well the relationship between drug exposure and treatment outcomes when compared to other approaches [15,16,17,18,19,20,21]

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