Scholarlink

Background <p>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.</p> Methods <p>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 &lt; 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.</p> Findings <p>A total of 737 samples from 185 individuals were included. Median CAB concentrations were 1,480&#xa0;µg/L (IQR: 1,097–1,955) vs. 1,180&#xa0;µg/L (879–1,570) for samples with HIV-1 RNA levels &lt; 20 copies/mL vs. ≥ 20 copies/mL, respectively (<i>p</i> = 0.001); for RPV, 77&#xa0;µg/L (53–107) vs. 63&#xa0;µg/L (47–87) (<i>p</i> = 0.001). Using ROC-derived thresholds, low concentrations of CAB (&lt; 1,240&#xa0;µg/L) or RPV (&lt; 76&#xa0;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.</p> Interpretation <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月4日

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

摘要

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.