Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus
Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus
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DOI：
10.1093/jac/dkx371
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发表时间：
2018-01-01
影响因子：
5.2
通讯作者：
Lazzarin, Adriano
中科院分区：
文献类型：
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作者：
Castagna, Antonella;Ferrara, Micol;Lazzarin, Adriano
目的：本研究利用临床实践数据，在为期5年的随访中评估了多替拉韦50mg每日两次在190名有抗逆转录病毒治疗经验且既往接触过第一代整合酶链转移抑制剂（INSTI）的HIV - 1治疗失败患者中的病毒学疗效。
患者和方法：该分析纳入了年龄≥18岁、有治疗经验、HIV - 1 RNA＞50拷贝/mL、携带INSTI耐药病毒且开始接受多替拉韦50mg每日两次加优化背景治疗（OBT）的HIV - 1感染患者，这些数据记录在国家前瞻性数据库PRESTIGIO（www.progetto prestigio.it）中。随访从开始使用多替拉韦50mg每日两次 + OBT直至出现病毒学失败（VF），或因任何原因停用多替拉韦，或最后一次接受多替拉韦50mg每日两次治疗的就诊。病毒学失败定义为在达到检测不到的病毒载量后，HIV - 1 RNA未能达到≤50拷贝/mL。
结果：自基线起12、24、36、48和60个月时，估计的病毒学失败概率分别为17%（95%置信区间 = 12% - 24%）、28%（95%置信区间 = 21% - 37%）、33%（95%置信区间 = 25% - 43%）、39%（95%置信区间 = 29% - 51%）和52%（95%置信区间 = 39% - 67%）。病毒学失败的较高风险独立与基线病毒载量＞100000拷贝/mL相关（调整后的风险比 = 4.73，95%置信区间 = 1.33 - 16.78，P = 0.016），并且与≥1个INSTI突变加上Q148H/K/R/N和G140S/A/C相比其他受试者相关（调整后的风险比 = 4.18，95%置信区间 = 1.32 - 13.23，P = 0.015）。
结论：我们的数据显示，在现实世界中，对于有治疗经验且治疗失败、携带INSTI耐药病毒的受试者，多替拉韦50mg每日两次联合OBT具有良好的长期疗效。在这一脆弱的受试者亚组中，密切监测依从性对于维持病毒学应答至关重要。
Objectives: This study evaluated the virological efficacy of dolutegravir 50 mg twice daily in 190 HIV-1 failing antiretroviral-experienced patients with previous exposure to first-generation integrase strand transfer inhibitor (INSTI) over a 5 year follow-up using data from clinical practice.Patients and methods: This analysis included HIV-1-infected patients who were >= 18 years of age, treatment experienced, had HIV-1 RNA > 50 copies/mL, with INSTI-resistant virus, who started dolutegravir 50 mg twice daily plus optimized background therapy (OBT), recorded in the national prospective database PRESTIGIO (www.proget toprestigio.it). Follow-up accrued from the start of dolutegravir 50 mg twice daily + OBT until virological failure (VF) or dolutegravir discontinuation for any reason or the last treatment visit on dolutegravir 50mg twice daily treatment. VF was defined by the lack of achievement of HIV-1 RNA = 50 copies/mL after achievement of undetectable viral load.Results: The estimated VF probabilities were 17% (95% CI = 12%-24%), 28% (95% CI = 21%-37%), 33% (95% CI = 25%-43%), 39% (95% CI = 29%-51%) and 52% (95% CI = 39%-67%) at 12, 24, 36, 48 and 60 months since baseline, respectively. A higher risk of VF was independently associated with baseline viral load >100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with >= 1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015).Conclusions: Our data showed a favourable long-term efficacy of dolutegravir 50 mg twice daily in association with OBT in treatment-experienced failing subjects, with INSTI-resistant virus, in the real world. A close monitoring of adherence is crucial for maintenance of virological response in this fragile subgroup of subjects.