Chaussade Hélène, Tumiotto Camille, Le Marec Fabien, Leleux Olivier, Lefèvre Lucile, Lazaro Estibaliz, Lafon Marie-Edith, Nyamankolly Elsa, Duffau Pierre, Neau Didier, Bellecave Pantxika, Bonnet Fabrice
CHU Bordeaux, Services de Médecine Interne et Maladies Infectieuses, Bordeaux, France.
CHU Bordeaux, Virology Laboratory, Bordeaux, France.
Open Forum Infect Dis. 2020 Nov 19;7(12):ofaa567. doi: 10.1093/ofid/ofaa567. eCollection 2020 Dec.
Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor (PI) indicated for the treatment of naïve and pretreated HIV-infected patients since 2007. Our study aims to describe DRV/r-treated patients experiencing virological failure (VF) documented with HIV resistance testing.
Data from patients belonging to the ANRS CO3 Aquitaine Cohort treated with a regimen including DRV/r between February 2007 and December 2015 were analyzed. Baseline characteristics of patients experiencing VF (defined by 2 consecutive plasma viral loads >50 copies/mL) were compared with those without VF. We then described factors associated with VF as emergence of IAS DRV resistance-associated mutations (RAMs).
Among the 1458 patients treated at least once with a DRV/r-based regimen, 270 (18.5%) patients experienced VF during follow-up, including 240 with at least 1 genotype resistance test (GRT). DRV RAMs were detected in 29 patients (12%). Among them, 25/29 patients had ≥2 DRV RAMs before DRV/r initiation, all of whom had experienced VF during previous PI treatments. For 18/29, DRV/r was maintained after VF, and controlled viremia was restored after modification of DRV-associated antiretroviral molecules or increased DRV dose. Finally, only 6/29 patients selected new DRV RAMs after DRV/r initiation. All of these experienced previous VFs while on other PIs.
These results highlight the efficacy and robustness of DRV/r, as the emergence of DRV RAMs appeared in <0.4% of patients receiving a DRV/r-based regimen in our large cohort.
自2007年起，利托那韦增强型达芦那韦（DRV/r）是一种蛋白酶抑制剂（PI），用于治疗初治和经治的HIV感染患者。我们的研究旨在描述经HIV耐药性检测记录的发生病毒学失败（VF）的DRV/r治疗患者。
分析了2007年2月至2015年12月期间接受含DRV/r方案治疗的ANRS CO3阿基坦队列患者的数据。将发生VF（定义为连续两次血浆病毒载量>50拷贝/mL）的患者的基线特征与未发生VF的患者进行比较。然后，我们描述了与VF相关的因素，即国际艾滋病协会（IAS）DRV耐药相关突变（RAMs）的出现。
在至少接受过一次基于DRV/r方案治疗的1458例患者中，270例（18.5%）患者在随访期间发生VF，其中240例进行了至少一次基因型耐药检测（GRT）。在29例患者（12%）中检测到DRV RAMs。其中，25/29例患者在开始使用DRV/r之前有≥2个DRV RAMs，所有这些患者在先前的PI治疗期间均发生了VF。对于18/29例患者，VF后继续使用DRV/r，在调整与DRV相关的抗逆转录病毒分子或增加DRV剂量后，病毒血症得到控制。最后，只有6/29例患者在开始使用DRV/r后出现了新的DRV RAMs。所有这些患者在使用其他PI时均经历过先前的VF。
这些结果突出了DRV/r的疗效和稳定性，因为在我们的大型队列中，接受基于DRV/r方案治疗的患者中DRV RAMs的出现率<0.4%。
