Capetti Amedeo F, Cossu Maria Vittoria, Orofino Giancarlo, Sterrantino Gaetana, Cenderello Giovanni, De Socio Giuseppe V, Cattelan Anna Maria, Soria Alessandro, Rusconi Stefano, Riccardi Niccolò, Baldin Gian Maria, Niero Fosca P, Barbarini Giorgio, Rizzardini Giuliano
1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Via Giovanni Battista Grassi, 74, pavillion 56, Malattie Infettive, 2nd floor, 20157, Milan, Italy.
1st Division of Infectious Diseases Amedeo di Savoia Hospital, Torino, Italy.
BMC Infect Dis. 2017 Sep 30;17(1):658. doi: 10.1186/s12879-017-2755-4.
Dolutegravir (DTG) plus darunavir/ritonavir (DRV/r) is a simple combination of drugs that has the best genetic barrier to HIV-1 resistance and may be fit for salvage therapy.
All HIV-1-infected subjects treated with DTG plus DRV/r between March 2014 and September 2015 in eight Italian centres were included in the analysis. The main metabolic data, efficacy parameters and safety data routinely collected were provided. This observational study is aimed to assess the efficacy of such approach. The primary end-point was the proportion of subjects achieving or maintaining virologic suppression <50 copies/mL at week 24. Secondary end points were maintaining virologic suppression in the follow-up (weeks 48 and 96) and safety.
One hundred and thirty subjects were followed for a median of 56 months. Reasons for switching were simplification (44.6%), viral failure (30%), toxicity (16.9%), non-adherence (4.6%), persistent low-level viremia (3.1%), and drug-drug interaction (0.8%). At baseline, 118 subjects had documented resistance to 1 to 5 antiretroviral classes while 12 had viral rebound at a time when genotypic tests were not yet available. Seventeen and 14 subjects took DRV/r and DTG twice daily, respectively. One subject was lost to follow-up, one discontinued for liver enzymes' elevation, one died of illicit drug abuse and one of cancer-related complications. The proportion of subjects with ongoing HIV replication dropped from 40% to 6.1%. Those with undetectable viral load increased from 38.5% to 76.2%. At week 48, 17.7% had HIV RNA between 1 and 49 copies/mL. The number of subjects with altered serum glucose, creatinine, ALT, AST, total-, HDL- and LDL-cholesterol, triglycerides and MDRD <90 mL/min decreased by week 48, while those having MDRD <60 mL/min remained 4.6%. Overall 90/283 baseline laboratory alterations returned to normality.
Switching to DTG plus DRV/r proved to be safe, suppressing viral replication without metabolic impact.
多替拉韦（DTG）联合达芦那韦/利托那韦（DRV/r）是一种简单的药物组合，对HIV-1耐药具有最佳的基因屏障，可能适用于挽救治疗。
纳入2014年3月至2015年9月期间在意大利8个中心接受DTG联合DRV/r治疗的所有HIV-1感染受试者进行分析。提供了常规收集的主要代谢数据、疗效参数和安全性数据。这项观察性研究旨在评估这种治疗方法的疗效。主要终点是在第24周时实现或维持病毒载量抑制<50拷贝/mL的受试者比例。次要终点是在随访期间（第48周和第96周）维持病毒载量抑制以及安全性。
130名受试者的中位随访时间为56个月。换药原因包括简化治疗方案（44.6%）、病毒学失败（30%）、毒性反应（16.9%）、依从性差（4.6%）、持续性低水平病毒血症（3.1%）和药物相互作用（0.8%）。基线时，118名受试者记录有对1至5类抗逆转录病毒药物耐药，而12名受试者在基因型检测尚未可用时出现病毒反弹。分别有17名和14名受试者每天服用两次DRV/r和DTG。1名受试者失访，1名因肝酶升高停药，1名死于药物滥用，1名死于癌症相关并发症。持续HIV复制的受试者比例从40%降至6.1%。病毒载量不可检测的受试者比例从38.5%增至76.2%。在第48周时，17.7%的受试者HIV RNA在1至49拷贝/mL之间。血清葡萄糖、肌酐、谷丙转氨酶、谷草转氨酶、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、甘油三酯和估计肾小球滤过率<90 mL/min的受试者数量在第48周时减少，而估计肾小球滤过率<60 mL/min的受试者比例仍为4.6%。总体而言，283项基线实验室指标改变中有90项恢复正常。
改用DTG联合DRV/r治疗被证明是安全的，可抑制病毒复制且无代谢影响。
