Winston Alan, Bloch Mark, Carr Andrew, Amin Janaki, Mallon Patrick W G, Ray John, Marriott Debbie, Cooper David A, Emery Sean
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, 2010, Australia.
J Antimicrob Chemother. 2005 Aug;56(2):380-7. doi: 10.1093/jac/dki235. Epub 2005 Jul 4.
Atazanavir is a recently approved HIV protease inhibitor (PI). As with other PIs, careful attention to potential pharmacokinetic drug interactions in clinical practice is necessary. The aim of this study was to assess the clinical associations with plasma atazanavir concentrations in HIV-positive individuals.
Individuals established on an atazanavir-containing regimen, completed an interviewer-administered questionnaire recording atazanavir dosing characteristics, concomitant medication use and adherence. After completion, plasma atazanavir concentrations were measured.
Of 100 individuals, mean trough plasma atazanavir concentrations (mug/L) were 282 (95% CI 95-468, n = 19) and 774 (95% CI 646-902, n = 81) in those on non- and ritonavir-boosted atazanavir regimens, respectively. Eighty-five individuals had HIV RNA <50 copies/mL. Seven individuals had atazanavir plasma concentrations below the assay limit of detection (<50 microg/L), all of whom had undetectable plasma HIV RNA. In a multivariate analysis, nevirapine use was associated with significantly lower trough atazanavir concentrations (P = 0.011) and lopinavir/ritonavir use with higher trough atazanavir concentrations (P = 0.032). Dosing characteristics (including food taken), concomitant medications (including drugs used for dyspepsia) and HIV RNA were not significantly associated with trough atazanavir concentrations.
In this cohort, despite the wide inter-individual variability of atazanavir trough concentrations, no significant association with dosing characteristics, concomitant medication (with the exception of nevirapine and lopinavir/ritonavir) or virological response was observed. Further work is needed to assess the optimal dosing regimen when using atazanavir with nevirapine.
阿扎那韦是一种最近获批的HIV蛋白酶抑制剂（PI）。与其他PI一样，在临床实践中需密切关注潜在的药代动力学药物相互作用。本研究的目的是评估HIV阳性个体中血浆阿扎那韦浓度的临床相关性。
采用含阿扎那韦方案治疗的个体，完成一份由访谈者填写的问卷，记录阿扎那韦给药特征、合并用药情况及依从性。完成后，测定血浆阿扎那韦浓度。
100名个体中，接受非利托那韦增强和利托那韦增强阿扎那韦方案治疗者的血浆阿扎那韦平均谷浓度（μg/L）分别为282（95%CI 95 - 468，n = 19）和774（95%CI 646 - 902，n = 81）。85名个体的HIV RNA<50拷贝/mL。7名个体的阿扎那韦血浆浓度低于检测下限（<50μg/L），所有这些个体的血浆HIV RNA均无法检测到。多变量分析中，使用奈韦拉平与较低的阿扎那韦谷浓度显著相关（P = 0.011），使用洛匹那韦/利托那韦与较高的阿扎那韦谷浓度相关（P = 0.032）。给药特征（包括进食情况）、合并用药（包括用于消化不良的药物）和HIV RNA与阿扎那韦谷浓度无显著相关性。
在该队列中，尽管阿扎那韦谷浓度存在较大的个体间差异，但未观察到与给药特征、合并用药（奈韦拉平和洛匹那韦/利托那韦除外）或病毒学反应有显著相关性。使用阿扎那韦和奈韦拉平时，需要进一步研究以评估最佳给药方案。
