在老年 HIV 感染者中，增效后的达芦那韦、度鲁特韦和拉米夫定的药代动力学特征。

Pharmacokinetic profiles of boosted darunavir, dolutegravir and lamivudine in aging people living with HIV.

机构信息

Service of Clinical Pharmacology, University Hospital of Lausanne and University of Lausanne, Lausanne Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel University of Basel, Basel Institute of Pharmaceutical Sciences of Western Switzerland, Geneva Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

出版信息

AIDS. 2020 Jan 1;34(1):103-108. doi: 10.1097/QAD.0000000000002372.

DOI:10.1097/QAD.0000000000002372

PMID:31490233

Abstract

OBJECTIVES

The pharmacokinetics of antiretroviral drugs may differ in elderly people living with HIV (PLWH) because of age-related physiological changes. We aimed to assess the pharmacokinetics of several antiretroviral drugs in aging PLWH enrolled in the Swiss HIV Cohort (SHCS).

DESIGN

Full pharmacokinetic profiling nested in a multicenter, observational, prospective cohort study. Additional collection of single point pharmacokinetic data during SHCS follow-up visits (unselected PLWH).

METHODS

PLWH were eligible for the full pharmacokinetics investigation if they were over the age of 55 years, on a stable boosted darunavir-containing or dolutegravir-containing regimen. Single point measurements were prospectively collected during SHCS follow-up visits to compare antiretroviral drug exposure in aging (≥65 years) and younger (<65 years) PLWH.

RESULTS

Nineteen PLWH with a median age of 64 years participated in the full pharmacokinetic investigations. Single point pharmacokinetic data were collected for 804 PLWH with a median age of 52 years. Boosted darunavir clearance was 40% lower in aging (≥65 years) compared with younger (<65 years) PLWH, consistent with other drugs predominantly metabolized by CYP3A. Dolutegravir exposure was similar between age groups whereas lamivudine exposure increased by 11% in aging PLWH. Median boosted darunavir, dolutegravir and lamivudine t1/2 were 148%, 45% and 32% higher in aging compared with younger PLWH.

CONCLUSION

Advanced age did not affect boosted darunavir exposure to a clinically significant extent despite the observed high variability in exposure. Age minimally affected dolutegravir and lamivudine exposure. Thus, dose adjustment based on age is a priori not warranted.

摘要

目的

由于与年龄相关的生理变化，抗逆转录病毒药物在老年艾滋病毒感染者（PLWH）中的药代动力学可能不同。我们旨在评估在瑞士艾滋病毒队列研究（SHCS）中入组的老年 PLWH 中几种抗逆转录病毒药物的药代动力学。

设计

在多中心、观察性、前瞻性队列研究中进行全面的药代动力学分析。在 SHCS 随访期间（未选择的 PLWH）额外收集单点药代动力学数据。

方法

如果年龄超过 55 岁且服用稳定的含增效达拉韦林或多替拉韦的方案，PLWH 有资格进行全面的药代动力学研究。在 SHCS 随访期间前瞻性收集单点测量值，以比较老年（≥65 岁）和年轻（<65 岁）PLWH 中抗逆转录病毒药物的暴露情况。

结果

19 名中位年龄为 64 岁的 PLWH 参加了全面的药代动力学研究。中位年龄为 52 岁的 804 名 PLWH 收集了单点药代动力学数据。与年轻（<65 岁）PLWH 相比，老年（≥65 岁）PLWH 中增效达拉韦林清除率降低了 40%，这与其他主要由 CYP3A 代谢的药物一致。两组间多替拉韦的暴露情况相似，而老年 PLWH 中拉米夫定的暴露量增加了 11%。与年轻 PLWH 相比，老年 PLWH 中增效达拉韦林、多替拉韦和拉米夫定的 t1/2 中位数分别高 148%、45%和 32%。