HIV 抗逆转录病毒治疗中每周 4 天方案成功的药理学数据（ANRS 162-4D 试验）。

Pharmacological data of a successful 4-days-a-week regimen in HIV antiretroviral therapy (ANRS 162-4D trial).

机构信息

Département de Pharmacologie-Toxicologie, Hôpitaux Universitaires Paris-Ile de France-Ouest, APHP, Hôpital Raymond Poincaré, MasSpecLab, Plateforme de spectrométrie de masse, Inserm U-1173, Université Versailles Saint Quentin-en-Yvelines, Garches, France.

Institut Pierre Louis d'Épidémiologie et de Santé Publique, Sorbonne Université, INSERM, Paris, France.

出版信息

Br J Clin Pharmacol. 2021 Apr;87(4):1930-1939. doi: 10.1111/bcp.14586. Epub 2020 Nov 5.

DOI:10.1111/bcp.14586

PMID:33010058

Abstract

INTRODUCTION

Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment.

OBJECTIVE

To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment.

METHODS

During a successful 48-week multicenter study (ANRS 162-4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by two nucleoside analogues and a third agent belonging to a boosted protease-inhibitor (PI, darunavir [DRV], atazanavir [ATV], lopinavir [LPV]) or a non-nucleoside-reverse-transcriptase inhibitor (NNRTI, efavirenz [EFV], etravirine [ETR], rilpivirine [RPV]) conducted in 100 patients (96% success), we determined the plasma concentrations of ARV. Blood samples were collected for analysis at inclusion (W0, 7/7 strategy for all patients), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF).

RESULTS

A total of 866 samples was analysed. Plasma concentrations were not statistically lower after 4 days (ON) vs 7/7 days of treatment except for RPV (-30 ng/mL at 4/7, P = 0.003). Significant lower plasma concentrations were observed for OFF vs ON except for ETR (n = 5, P = 0.062). Overall, 87.1% of ON concentrations (ATV 92.1%, DRV 51.1%, LPV 62.5%, EFV 94.4%, ETR 100% and RPV 94.9%) and 21.8% of OFF concentrations (ATV 1.4%, DRV 0.0%, LPV 0.0%, EFV 16.0%, ETR 92.6% and RPV 39.0%) were above the theoretical limit of efficacy of the molecule. In the OFF period, 85.8% of PI concentrations were under the limit of quantification, while 98.0% of NNRTI concentrations were quantifiable.

CONCLUSION

Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.

摘要

简介

间歇性治疗期间，抗逆转录病毒治疗（ARV）的血浆浓度数据有限。

目的

比较治疗期间多个时间点的停药（OFF）和用药（ON）期间的血浆浓度。

方法

在一项成功的 48 周多中心研究（ANRS 162-4D 试验）中，100 名接受两种核苷类似物和第三种增效蛋白酶抑制剂（PI，达芦那韦[DRV]、阿扎那韦[ATV]、洛匹那韦[LPV]）或非核苷逆转录酶抑制剂（NNRTI，依非韦伦[EFV]、依曲韦林[ETR]、利匹韦林[RPV]）治疗的成年患者，每 4 天接受治疗（ON），然后停药 3 天（OFF）。在所有患者中采用 7/7 方案（W0）采血进行分析，ON 时采集 W16 和 W40 时间点的血样，OFF 时采集 W4、W8、W12、W24、W32 和 W48 时间点的血样。

结果

共分析了 866 份样本。除 RPV 外（ON 时为 4/7，低于 30ng/ml，P = 0.003），4 天（ON）与 7/7 天治疗后，血浆浓度无统计学差异。除 ETR 外（n = 5，P = 0.062），OFF 时的血浆浓度显著低于 ON 时。总体而言，ON 时的浓度有 87.1%（ATV 为 92.1%，DRV 为 51.1%，LPV 为 62.5%，EFV 为 94.4%，ETR 为 100%，RPV 为 94.9%）和 21.8%（ATV 为 1.4%，DRV 为 0.0%，LPV 为 0.0%，EFV 为 16.0%，ETR 为 92.6%，RPV 为 39.0%）的 OFF 时浓度超过分子的理论疗效下限。在 OFF 期，85.8%的 PI 浓度低于定量下限，而 98.0%的 NNRTI 浓度可定量。