在接受度鲁特韦/利匹韦林双药维持治疗的 HIV-1 感染患者队列中，治疗药物监测和第 48 周的病毒学应答（ANRS-MIE-BIRIDER 研究）。

Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study).

机构信息

Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, Rennes, France.

MPFRPV, Université de Franche-Comté, Besançon, France.

出版信息

Br J Clin Pharmacol. 2024 Jan;90(1):264-273. doi: 10.1111/bcp.15890. Epub 2023 Sep 18.

DOI:10.1111/bcp.15890

PMID:37602480

Abstract

AIMS

Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV-1 RNA viral load (VL) during maintenance dual therapy.

METHODS

We performed a retrospective analysis of DTG and RPV therapeutic drug monitoring in people living with HIV/AIDS (PLWHA) with dual therapy in 9 French centres. DTG and RPV trough plasma concentrations were estimated using a Bayesian approach to predict Cmin. The relationship between the pharmacokinetics of DTG and RPV and VL > 50 copies (cp)/mL was explored using joint nonlinear mixed models. The frequency of subtherapeutic threshold (DTG Cmin below 640 ng/mL and RPV Cmin below 50 ng/mL) were compared between PLWHA presenting VL > 50 cp/mL or not during the study.

RESULTS

At baseline, 209 PLWHA were enrolled in the study. At week 48, 19 people living with HIV/AIDS (9.1%) discontinued their treatment and 15 PLWHA (7.1%) exhibited VL > 50 cp/mL. Six PLWHA out of 15 (40.0%) with VL > 50 cp/mL during the follow-up had at least 1 Cmin below the respective thresholds while only 26/194 patients (13.4%) without virological replication had at least 1 concentration below the threshold (P = .015).

CONCLUSION

A majority of PLWHA receiving DTG/RPV maintenance dual therapy demonstrated VL < 50 cp/mL but virological replication was more frequent in people living with HIV/AIDS with subtherapeutic Cmin.

摘要

目的

多替拉韦（DTG）和利匹韦林（RPV）联合治疗目前被推荐作为病毒学抑制的 HIV 患者的一种转换选择。文献表明，联合治疗发生病毒学失败可能与治疗药物浓度低于治疗范围有关。在本研究中，我们旨在描述接受 DTG 和 RPV 维持联合治疗的 HIV 感染者/艾滋病患者（PLWHA）的 DTG 和 RPV 谷浓度（Cmin）和血浆 HIV-1 RNA 病毒载量（VL）。

方法

我们对 9 个法国中心的 209 例接受 DTG 和 RPV 维持联合治疗的 PLWHA 进行了 DTG 和 RPV 治疗药物监测的回顾性分析。采用贝叶斯方法估计 DTG 和 RPV 的 Cmin。采用联合非线性混合模型探讨 DTG 和 RPV 的药代动力学与 VL＞50 拷贝（cp）/mL 的关系。比较研究期间 VL＞50 cp/mL 与不＞50 cp/mL 的 PLWHA 出现治疗药物浓度低于治疗范围下限（DTG Cmin＜640ng/mL 和 RPV Cmin＜50ng/mL）的频率。

结果

在基线时，209 例 PLWHA 入组本研究。在第 48 周，19 例 PLWHA（9.1%）停止治疗，15 例 PLWHA（7.1%）出现 VL＞50 cp/mL。在随访期间，15 例（40.0%）VL＞50 cp/mL 的患者中有 6 例至少有 1 次 Cmin 低于相应的阈值，而 194 例无病毒学复制的患者中仅有 26 例（13.4%）至少有 1 次浓度低于阈值（P＝0.015）。