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长效卡博特韦和rilpivirine的真实世界谷浓度及有效性：瑞士的一项多中心前瞻性观察研究

Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland.

作者信息

Thoueille Paul, Saldanha Susana Alves, Schaller Fabian, Choong Eva, Munting Aline, Cavassini Matthias, Braun Dominique, Günthard Huldrych F, Kusejko Katharina, Surial Bernard, Furrer Hansjakob, Rauch Andri, Rougemont Mathieu, Ustero Pilar, Calmy Alexandra, Stöckle Marcel, Marzolini Catia, Di Benedetto Caroline, Bernasconi Enos, Schmid Patrick, Piso Rein Jan, Andre Pascal, Girardin François R, Guidi Monia, Buclin Thierry, Decosterd Laurent A

机构信息

Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

出版信息

Lancet Reg Health Eur. 2023 Dec 13;36:100793. doi: 10.1016/j.lanepe.2023.100793. eCollection 2024 Jan.

DOI:10.1016/j.lanepe.2023.100793
PMID:38162253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10757247/
Abstract

BACKGROUND: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. METHODS: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023. FINDINGS: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load. INTERPRETATION: Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated. FUNDING: This work was funded by the Swiss National Science Foundation, grant number N 324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).

摘要

背景：长效卡博特韦和利匹韦林的疗效及耐受性已在III期试验中得到证实。然而，低浓度与其他风险因素相结合与病毒学失败风险增加相关。本研究旨在验证在真实世界环境中测得的药物浓度是否与先前报道的一致。 方法：SHCS - 879是瑞士艾滋病毒队列研究中的一项全国性观察性研究，用于监测接受长效卡博特韦加利匹韦林治疗的艾滋病毒感染者（PWH）。样本采集时间为2022年3月至2023年3月。 研究结果：总体而言，从186名PWH中获取了725份样本。我们的数据显示，卡博特韦和利匹韦林浓度存在较大的个体间差异，一些个体反复出现低浓度情况。利匹韦林谷浓度与III期试验结果一致，而卡博特韦浓度较低。第一个浓度四分位数仅略高于664 ng/mL的目标值。探索性统计分析发现，男性的卡博特韦谷浓度比女性低35%（p < 0.01）。总体而言，172名PWH（92%）病毒载量仍受到抑制，3人经历了病毒学失败（1.6%），其中2人药物暴露不理想。未发现谷浓度低与可检测到的病毒载量之间存在关联。 解读：真实世界中的卡博特韦浓度显著低于先前报道。然而，这些浓度似乎足以确保几乎每个PWH都能实现持续的病毒学抑制。这些令人安心的数据对迄今为止采用的较为保守的阈值提出了挑战，这些阈值可能引发不必要的担忧。然而，我们的研究表明，一些PWH反复出现极低的药物水平，原因尚待阐明。 资金来源：本研究由瑞士国家科学基金会资助，资助编号为N 324730_192449。本研究未获得制药行业的支持。本研究是在瑞士艾滋病毒队列研究框架内进行的，得到了瑞士国家科学基金会（资助编号#201369）、SHCS项目#879以及SHCS研究基金会的支持。SHCS数据由瑞士五所大学医院、两所州立医院、15家附属医院和36名私人医生收集（名单见http://www.shcs.ch/180 - health - care - providers）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c9f/10757247/fc0157f3277d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c9f/10757247/34c4e7a68485/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c9f/10757247/fc0157f3277d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c9f/10757247/34c4e7a68485/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c9f/10757247/fc0157f3277d/gr2.jpg

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Viruses. 2025-8-12

[2]
Brief Report: Switching to Long-Acting CAB/RPV: Data From an Italian Monocentric Cohort.

J Acquir Immune Defic Syndr. 2024-12-1

[3]
Optimizing the Use of Cabotegravir Plus Rilpivirine Long-acting Therapy in HIV Care: Evidence, Implementation, and Unanswered Questions.

Open Forum Infect Dis. 2025-7-3

[4]
Long-Term Real-World Use of Cabotegravir/Rilpivirine: Adherence and Virological Efficacy over a 44-Month Observation Period.

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[5]
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Open Forum Infect Dis. 2025-6-11

[6]
Long-acting injectable cabotegravir and rilpivirine in observational cohort studies: A systematic review on virological failure, resistance and re-suppression outcomes in virally suppressed individuals living with HIV.

HIV Med. 2025-8

[7]
Influence of patient characteristics and oral lead-in on long-acting cabotegravir and rilpivirine pharmacokinetics and outcomes in people with HIV: a real-world study.

Antimicrob Agents Chemother. 2025-7-2

[8]
Long-Acting Injectable Antiretroviral Therapy for Treatment of Human Immunodeficiency Virus: A Review.

Curr HIV/AIDS Rep. 2025-4-23

[9]
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[10]
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本文引用的文献

[1]
Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure.

Clin Infect Dis. 2023-11-17

[2]
Long-Acting Cabotegravir and Rilpivirine Dosed Every 2 Months in Adults With Human Immunodeficiency Virus 1 Type 1 Infection: 152-Week Results From ATLAS-2M, a Randomized, Open-Label, Phase 3b, Noninferiority Study.

Clin Infect Dis. 2023-5-3

[3]
A population pharmacokinetic model based on HPTN 077 of long-acting injectable cabotegravir for HIV PrEP.

Br J Clin Pharmacol. 2022-10

[4]
Population pharmacokinetics of cabotegravir following administration of oral tablet and long-acting intramuscular injection in adult HIV-1-infected and uninfected subjects.

Br J Clin Pharmacol. 2022-10

[5]
Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study.

Lancet HIV. 2021-11

[6]
Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV.

J Antimicrob Chemother. 2021-11-12

[7]
Cohort Profile Update: The Swiss HIV Cohort Study (SHCS).

Int J Epidemiol. 2022-2-18

[8]
Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis.

AIDS. 2021-7-15

[9]
Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study.

Lancet. 2021-12-19

[10]
Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial.

Lancet HIV. 2020-6-1

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