Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milano, Italy.
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
J Antimicrob Chemother. 2018 Jan 1;73(1):177-182. doi: 10.1093/jac/dkx371.
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.
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.progettoprestigio.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 50 mg twice daily treatment. VF was defined by the lack of achievement of HIV-1 RNA <50 copies/mL by 6 months and thereafter, or the occurrence of two consecutive HIV-1 RNA ≥50 copies/mL after achievement of undetectable viral load.
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).
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.
本研究通过对 190 名既往使用过第一代整合酶抑制剂（INSTI）的经治 HIV-1 失败患者进行 5 年随访，评估每日两次使用 50mg 度鲁特韦的病毒学疗效，这些患者在临床实践中均具有 HIV-1 RNA>50 拷贝/mL，且存在对 INSTI 耐药的病毒。
本分析纳入≥18 岁、有治疗史、HIV-1 RNA>50 拷贝/mL、存在 INSTI 耐药病毒、开始每日两次使用 50mg 度鲁特韦加优化背景治疗（OBT）的 HIV-1 感染患者，这些患者来自国家前瞻性数据库 PRESTIGIO（www.progettoprestigio.it）。从开始使用度鲁特韦 50mg 每日两次+OBT 起，随访至病毒学失败（VF）或因任何原因停用度鲁特韦，或至最后一次度鲁特韦 50mg 每日两次治疗的就诊日期。VF 定义为 6 个月时及之后未能达到 HIV-1 RNA<50 拷贝/mL，或在达到不可检测病毒载量后连续两次 HIV-1 RNA≥50 拷贝/mL。
自基线起 12、24、36、48 和 60 个月时的估计 VF 概率分别为 17%（95%CI=12%-24%）、28%（95%CI=21%-37%）、33%（95%CI=25%-43%）、39%（95%CI=29%-51%）和 52%（95%CI=39%-67%）。VF 的风险较高与基线病毒载量>100000 拷贝/mL（校正 HR=4.73，95%CI=1.33-16.78，P=0.016）和与除其他患者以外具有≥1 个 INSTI 突变，以及 Q148H/K/R/N 和 G140S/A/C 突变相关（校正 HR=4.18，95%CI=1.32-13.23，P=0.015）。
我们的数据显示，在真实世界中，对于存在 INSTI 耐药病毒的经治失败患者，每日两次使用 50mg 度鲁特韦联合 OBT 具有良好的长期疗效。在这一脆弱的亚组患者中，密切监测依从性对于维持病毒学反应至关重要。
