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Research article
Bernard NGARA
University of Zimbabwe College of Health Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8355-5954
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This work is licensed under a CC BY 4.0 License. Read Full License
Background Adolescents 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.
Methods We based the study on secondary data analysis whereby data from a previous study on Zimbabwean adolescents which collected hair samples at enrolment and three months follow-up was used in model development. We performed model development in NONMEM (version 7.3) ADVAN 13.
Results There 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.
Conclusion The 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.
Keywords
Pharmacokinetic modelling, HIV/AIDS, Adolescents, Adherence, Hair, NONMEM
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CURRENT STATUS: Published
View the published article at BMC Pharmacology and Toxicology.
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Posted 31 Jul, 2020
No community comments so far
Submission checks complete
On 27 Jul, 2020
Editorial decision: Accept
On 27 Jul, 2020
Editor assigned
On 26 Jul, 2020
Editor invited
On 25 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 22 Jul, 2020
Review #1 received
Received 21 Jul, 2020
Reviewer #1 agreed
On 24 Jun, 2020
Reviewers invited
Invitations sent on 23 Jun, 2020
Editor assigned
On 04 Jun, 2020
Submission checks complete
On 03 Jun, 2020
Editor invited
On 03 Jun, 2020
No comments provided
Editorial decision: Major revision
On 12 May, 2020
Review #2 received
Received 07 May, 2020
Reviewer #2 agreed
On 13 Apr, 2020
Review #1 received
Received 03 Apr, 2020
Reviewer #1 agreed
On 19 Mar, 2020
Reviewers invited
Invitations sent on 15 Mar, 2020
Editor assigned
On 24 Feb, 2020
Submission checks complete
On 23 Feb, 2020
Editor invited
On 23 Feb, 2020
First submitted
On 20 Feb, 2020
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See the published version of this preprint at BMC Pharmacology and Toxicology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Bernard NGARA
University of Zimbabwe College of Health Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8355-5954
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Pharmacology and Toxicology.
Version 3
Posted 31 Jul, 2020
No community comments so far
Submission checks complete
On 27 Jul, 2020
Editorial decision: Accept
On 27 Jul, 2020
Editor assigned
On 26 Jul, 2020
Editor invited
On 25 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 22 Jul, 2020
Review #1 received
Received 21 Jul, 2020
Reviewer #1 agreed
On 24 Jun, 2020
Reviewers invited
Invitations sent on 23 Jun, 2020
Editor assigned
On 04 Jun, 2020
Submission checks complete
On 03 Jun, 2020
Editor invited
On 03 Jun, 2020
No comments provided
Editorial decision: Major revision
On 12 May, 2020
Review #2 received
Received 07 May, 2020
Reviewer #2 agreed
On 13 Apr, 2020
Review #1 received
Received 03 Apr, 2020
Reviewer #1 agreed
On 19 Mar, 2020
Reviewers invited
Invitations sent on 15 Mar, 2020
Editor assigned
On 24 Feb, 2020
Submission checks complete
On 23 Feb, 2020
Editor invited
On 23 Feb, 2020
First submitted
On 20 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Pharmacology and Toxicology.
Background Adolescents 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.
Methods We based the study on secondary data analysis whereby data from a previous study on Zimbabwean adolescents which collected hair samples at enrolment and three months follow-up was used in model development. We performed model development in NONMEM (version 7.3) ADVAN 13.
Results There 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.
Conclusion The 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.
Figure 1
Figure 2
This preprint is available for download as a PDF.
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