Noe Sebastian, Ivanova Anna, Schabaz Farhad, von Krosigk Ariane E, Wiese Carmen, Wolf Eva, Jonson-Oldenbuettel Celia
HIV Research and Clinical Care, Medizinisches Versorgungszentrum München am Goetheplatz, Munich, DEU.
I-BioStat, Hasselt University, Hasselt, BEL.
Cureus. 2025 Jan 2;17(1):e76829. doi: 10.7759/cureus.76829. eCollection 2025 Jan.
Background Virologic failure (VF) is still a major concern in the use of cabotegravir (CAB) and rilpivirine (RPV) long-acting (LA) for many healthcare professionals (HCP). While many results from clinical trials have been published, there is suspicion that they might underestimate the risk under less-controlled real-life conditions. This study aimed to estimate the probability of VF (primary objective) as well as discontinuation for any reason (secondary objective) among people with HIV (PWH) on CAB and RPV LA every two months (Q2M) in real life using Bayesian methodology. Methods Bayesian estimation of VF based on prior knowledge about VF and discontinuation on CAB and RPV Q2M from randomized controlled trials (ATLAS-2M, SOLAR) and real-world data from CAB and RPV LA from a large single-center cohort. Results Among 175 PWH, two (1.1%) met the criteria of VF through week 48 (W48), resulting in an estimated risk of VF at W48 of 1.2% [0.6%; 1.9%] using Bayesian estimation. In one of the PWH, two-class resistance was observed at the time of VF, most likely being therapy emerging. The probability of discontinuation for any reason by W48 was 21.4%, leading to a Bayesian risk estimate of 8.9% [7.3%; 10.5%]. The main reasons for discontinuation were injection-site reactions (n=10). Conclusions Risk of VF on CAB and RPV LA under real-life conditions seems to be comparable to results in clinical trials. This finding can be reassuring for both PWH and HCPs considering CAB and RPV LA as an alternative to oral antiretroviral treatment, particularly when considering the risk factors for VF that have been identified from the cases of VF in the clinical trials for patient selection. At the same time, rates of discontinuation may be considerably higher. However, this does not seem to be an indicator of a worse safety profile outside clinical trials, but probably could be the result of making CAB and RPV LA available to a wider population of PWH.
对于许多医疗保健专业人员（HCP）而言，在使用卡博特韦（CAB）和利匹韦林（RPV）长效（LA）制剂时，病毒学失败（VF）仍是一个主要问题。虽然已发表了许多临床试验结果，但有人怀疑这些结果可能低估了在控制较差的现实生活条件下的风险。本研究旨在使用贝叶斯方法估计在现实生活中每两个月（Q2M）接受CAB和RPV LA治疗的艾滋病毒感染者（PWH）中VF的概率（主要目标）以及因任何原因停药的概率（次要目标）。
基于随机对照试验（ATLAS - 2M、SOLAR）中关于CAB和RPV Q2M的VF和停药的先验知识以及来自一个大型单中心队列的CAB和RPV LA的真实世界数据，对VF进行贝叶斯估计。
在175名PWH中，到第48周（W48）时，有两名（1.1%）符合VF标准，使用贝叶斯估计得出W48时VF的估计风险为1.2%[0.6%；1.9%]。在其中一名PWH中，VF时观察到二级耐药，很可能是治疗中出现的。到W48时因任何原因停药的概率为21.4%，贝叶斯风险估计为8.9%[7.3%；10.5%]。停药的主要原因是注射部位反应（n = 10）。
在现实生活条件下，CAB和RPV LA的VF风险似乎与临床试验结果相当。这一发现对于考虑将CAB和RPV LA作为口服抗逆转录病毒治疗替代方案的PWH和HCP来说都可以令人安心，特别是在考虑从临床试验中VF病例确定的VF风险因素以进行患者选择时。同时，停药率可能会高得多。然而，这似乎并不是临床试验之外安全性较差的指标，而可能是由于CAB和RPV LA可供更广泛的PWH人群使用的结果。
