Ngara Bernard, Zvada Simbarashe, Chawana Tariro Dianah, Stray-Pedersen Babill, Nhachi Charles Fungai Brian, Rusakaniko Simbarashe
Department of Community Medicine, University of Zimbabwe College of Health Sciences, Mazowe Street, Parirenyatwa Complex, P. O Box A178 Avondale, Harare, Zimbabwe.
Department of Clinical Pharmacology, Stellenbosch University, Private Bag X1, Matieland, Stellenbosch, 7602, South Africa.
BMC Pharmacol Toxicol. 2020 Aug 3;21(1):58. doi: 10.1186/s40360-020-00437-y.
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.
We 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.
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.
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.
青少年在艾滋病毒治疗中的不依从性较高。头发中的药物浓度有望成为评估抗逆转录病毒（ARV）药物暴露情况的可靠指标。药代动力学建模可以探索头发中药物的效用。我们旨在开发并验证基于阿扎那韦/利托那韦（ATV/r）在头发中的药代动力学模型，并确定与头发蓄积变异性相关的因素。
我们基于二次数据分析开展本研究，将之前一项针对津巴布韦青少年的研究数据用于模型开发，该研究在入组时和随访3个月时收集了头发样本。我们在NONMEM（版本7.3）ADVAN 13中进行模型开发。
头发中ATV/r各自的含量分别占稳态谷血浆浓度的16%/18%。在随访时，我们估计头发中ATV/r各自的含量增加了30%/42%。我们发现依从性评分每增加一个单位，头发中ATV/r的浓度就增加2%。与正常体重的参与者相比，体型较瘦的参与者头发中的阿扎那韦含量高54%，而超重者则低21%。由兄弟姐妹提供护理的青少年头发中的阿扎那韦含量比其他护理形式的青少年至少低54%。
我们的分析中发现头发中ATV/r浓度增加的决定因素是随访事件监测、体重指数和护理者状况。测量头发中的药物浓度是可行的，并且对于监测抗逆转录病毒药物暴露可能更准确。
