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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Posted 31 Jul, 2020
On 03 Aug, 2020
On 27 Jul, 2020
On 27 Jul, 2020
On 26 Jul, 2020
On 25 Jul, 2020
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Received 21 Jul, 2020
On 24 Jun, 2020
Invitations sent on 23 Jun, 2020
On 04 Jun, 2020
On 03 Jun, 2020
On 03 Jun, 2020
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Received 07 May, 2020
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Received 03 Apr, 2020
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On 24 Feb, 2020
On 23 Feb, 2020
On 23 Feb, 2020
On 20 Feb, 2020
Posted 31 Jul, 2020
On 03 Aug, 2020
On 27 Jul, 2020
On 27 Jul, 2020
On 26 Jul, 2020
On 25 Jul, 2020
On 22 Jul, 2020
Received 21 Jul, 2020
On 24 Jun, 2020
Invitations sent on 23 Jun, 2020
On 04 Jun, 2020
On 03 Jun, 2020
On 03 Jun, 2020
On 12 May, 2020
Received 07 May, 2020
On 13 Apr, 2020
Received 03 Apr, 2020
On 19 Mar, 2020
Invitations sent on 15 Mar, 2020
On 24 Feb, 2020
On 23 Feb, 2020
On 23 Feb, 2020
On 20 Feb, 2020
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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