Lathouwers Erkki, De La Rosa Guy, Van de Casteele Tom, Baeten Benny, Tomaka Frank, De Meyer Sandra, Picchio Gaston
Janssen Infectious Diseases - Diagnostics BVBA, Beerse, Belgium.
Antivir Ther. 2013;18(3):289-300. doi: 10.3851/IMP2569. Epub 2013 Apr 4.
The aim of this analysis was to characterize viral resistance in the Phase III, randomized ODIN trial, which demonstrated non-inferiority of once-daily darunavir/ritonavir (DRV/r) 800/100 mg to DRV/r 600/100 mg twice daily, each combined with an optimized background regimen in treatment-experienced patients with no DRV resistance-associated mutations (RAMs) at screening.
Virological failure (VF) was defined as never achieving or losing confirmed virological suppression after week 12, with patients being classed as 'never suppressed' (never achieved HIV-1 RNA<50 copies/ml) or 'rebounders' (achieved two consecutive HIV-1 RNA<50 copies/ml but then ≥ 50 copies/ml). Phenotypes and genotypes of plasma HIV-1 viruses, using population-based sequencing and Antivirogram(®), were determined at screening/baseline and on samples from VFs with HIV-1 RNA ≥ 50 copies/ml.
Mean baseline HIV-1 RNA was 4.16 log10 copies/ml and 53.9% of patients were protease inhibitor (PI)-experienced at enrolment. VF rate was similar in both arms. A similar proportion of virologically failing patients in both arms developed PI RAMs (11.7% versus 9.5%, respectively) or nucleoside reverse transcriptase inhibitor RAMs (6.7% versus 7.1%). One patient with VF (once-daily arm) developed four primary PI mutations, three of which were also DRV RAMs. This patient was also the only VF to lose susceptibility to DRV. Loss of susceptibility to other PIs (once daily 3.4%; twice daily 0%) and nucleoside reverse transcriptase inhibitors (once daily 13.6%; twice daily 9.8%) in VF patients was infrequent and comparable between treatment arms.
These analyses showed once-daily DRV/r 800/100 mg was associated with similar rates of VF and emergence of resistance as DRV/r 600/100 mg twice daily in treatment-experienced patients with no DRV RAMs.
本分析的目的是在III期随机ODIN试验中对病毒耐药性进行特征分析，该试验证明，对于筛选时无达芦那韦（DRV）耐药相关突变（RAMs）的经治患者，每日一次服用800/100mg达芦那韦/利托那韦（DRV/r）不劣于每日两次服用600/100mg DRV/r，二者均联合优化背景治疗方案。
病毒学失败（VF）定义为在第12周后从未实现或失去已确认的病毒学抑制，患者分为“从未被抑制”（从未实现HIV-1 RNA<50拷贝/ml）或“复发者”（连续两次实现HIV-1 RNA<50拷贝/ml，但随后≥50拷贝/ml）。在筛选/基线时以及HIV-1 RNA≥50拷贝/ml的VF样本上，使用群体测序和Antivirogram(®)测定血浆HIV-1病毒的表型和基因型。
平均基线HIV-1 RNA为4.16 log10拷贝/ml，53.9%的患者在入组时曾接受过蛋白酶抑制剂（PI）治疗。两组的VF率相似。两组中病毒学失败患者出现PI RAMs的比例相似（分别为11.7%和9.5%）或核苷类逆转录酶抑制剂RAMs的比例相似（6.7%和7.1%）。一名VF患者（每日一次治疗组）出现了4种主要PI突变，其中3种也是DRV RAMs。该患者也是唯一对DRV失去敏感性的VF患者。VF患者中对其他PI（每日一次3.4%；每日两次0%）和核苷类逆转录酶抑制剂（每日一次13.6%；每日两次9.8%）失去敏感性的情况很少见，且治疗组之间相当。
这些分析表明，对于无DRV RAMs的经治患者，每日一次服用800/100mg DRV/r与每日两次服用600/100mg DRV/r的VF率和耐药性出现率相似。
