Trough concentrations of cabotegravir and rilpivirine and their association with detectable viral load in people with HIV on long-acting treatment.

IF 5.4 2区医学 Q1 INFECTIOUS DISEASES

Infection Pub Date : 2025-07-04 DOI:10.1007/s15010-025-02577-x

Sebastian Noe, Ulrich Seybold, Farhad Schabaz, Ariane von Krosigk, Carmen Wiese, Eva Wolf, Celia Jonsson-Oldenbüttel, Anna Ivanova

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引用次数: 0

Abstract

Background: Cabotegravir (CAB) and rilpivirine (RPV) constitute the first complete non-oral ART regimen for HIV-1 treatment. Due to virologic failure (VF) with resistance in clinical trials, concerns persist regarding broader use in clinical practice. In particular, the role of trough drug concentrations in relation to viremia and VF remains unclear. This study explored the association between CAB and RPV trough concentrations in a retrospective, single-center study.

Methods: We retrospectively analyzed data from the HIV research and clinical care center MVZ München am Goetheplatz, Germany. Inclusion criteria were CAB and RPV long-acting therapy every 8 weeks without additional ART and availability of drug concentrations within 7 days before the next administration. A modified Wilcoxon test assessed differences in concentrations between samples with HIV-1 RNA < 20 vs. ≥20 copies/mL. Odds ratios (ORs) were estimated using generalized estimation equation (GEE) models, and ROC analysis identified potential alternative drug concentration thresholds.

Findings: A total of 737 samples from 185 individuals were included. Median CAB concentrations were 1,480 µg/L (IQR: 1,097-1,955) vs. 1,180 µg/L (879-1,570) for samples with HIV-1 RNA levels < 20 copies/mL vs. ≥ 20 copies/mL, respectively (p = 0.001); for RPV, 77 µg/L (53-107) vs. 63 µg/L (47-87) (p = 0.001). Using ROC-derived thresholds, low concentrations of CAB (< 1,240 µg/L) or RPV (< 76 µg/L) were found in 11.5% and 25.4% of samples, respectively, and associated with ORs of 2.4 (1.5-4.0) and 2.3 (1.4-3.8) for HIV-1 RNA ≥ 20 copies/mL.

Interpretation: Lower CAB and RPV concentrations were associated with viremia, particularly using the ROC-derived thresholds. Among individuals with VF and available drug concentration data, 87.5% had at least one drug below these thresholds. Further research on therapeutic drug monitoring is warranted.

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长效治疗的HIV患者卡波特韦和利匹韦林的谷浓度及其与可检测病毒载量的关系

背景：卡波特韦（CAB）和利匹韦林（RPV）构成了第一个完整的非口服抗逆转录病毒治疗方案。由于临床试验中的病毒学失败（VF）和耐药性，人们对在临床实践中更广泛使用的担忧仍然存在。特别是，谷药浓度在病毒血症和VF中的作用尚不清楚。本研究通过一项回顾性、单中心研究探讨了CAB和RPV谷浓度之间的关系。方法：我们回顾性分析来自德国MVZ m研究和临床护理中心（MVZ m研究和临床护理中心）的数据。纳入标准为每8周进行一次CAB和RPV长效治疗，无额外ART治疗，并在下次给药前7天内获得药物浓度。改良的Wilcoxon试验评估了具有HIV-1 RNA发现的样本之间的浓度差异：来自185个个体的737个样本被纳入。HIV-1 RNA水平样品的中位CAB浓度为1480µg/L (IQR: 1097 - 1955)，而HIV-1 RNA水平样品的中位CAB浓度为1180µg/L （IQR: 879- 1570）。解释：较低的CAB和RPV浓度与病毒血症相关，特别是使用roc衍生阈值。在有VF和现有药物浓度数据的个体中，87.5%至少有一种药物低于这些阈值。治疗药物监测的进一步研究是必要的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection 医学-传染病学

CiteScore

12.50

自引率

1.30%

发文量

224

审稿时长

6-12 weeks

期刊介绍： Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings. The journal covers a wide range of topics, including: Etiology: The study of the causes of infectious diseases. Pathogenesis: The process by which an infectious agent causes disease. Diagnosis: The methods and techniques used to identify infectious diseases. Treatment: The medical interventions and strategies employed to treat infectious diseases. Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies. Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections. In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.