Imaz Arkaitz, del Saz Sara Villar, Ribas M Angels, Curran Adrian, Caballero Estrella, Falcó Vicenç, Crespo Manel, Ocaña Inma, Diaz Marjorie, de Gopegui Enrique Ruiz, Riera Melcior, Ribera Esteban
Infectious Diseases Department, Hospital Universitari Vall d'Hebron and Departament de Medicina, Universidad Autónoma de Barcelona, Barcelona, Spain.
J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):382-6. doi: 10.1097/QAI.0b013e3181b17f53.
Boosted darunavir (DRV/r) plus etravirine (ETR), in DUET trials, and raltegravir, in BENCHMRK trials, showed high rates of virologic response in patients with multidrug-resistant HIV-1 infection, particularly when associated with two more fully active antiretroviral drugs. No data from clinical trials, about this combination, are available.
Thirty-two consecutive heavily pretreated patients with multidrug-resistant HIV-1 infection who started a new salvage regimen with RAL (400 mg twice daily), ETR (200 mg twice daily), and DRV/r (600/100 mg twice daily) were studied. Clinical evaluation and immunologic, virologic, and biochemical parameters were collected at baseline and at Weeks 4, 12, and 24.
Median baseline characteristics were age 44 years, 13 years on antiretroviral therapy, nine prior highly active antiretroviral therapy regimens, 261 CD4 cells/mL, and HIV-1 RNA 4.2 log10 copies/mL. Sixteen (50%) and 14 (44%) patients were enfuvirtide- and tipranavir-experienced, respectively. Three-class resistance mutations were present in all patients. Three patients (9%) had isolates with three ETR resistance mutations. All patients were DRV-naïve with a median of one DRV resistance mutation. At Weeks 4, 12, and 24, respectively, 63%, 81%, and 94% of patients achieved HIV1-RNA less than 50 copies/mL. Median CD4 cell count increased 30, 73, and 103 cells/mL at Weeks 4, 12, and 24, respectively. No patient had adverse events leading to discontinuation of the regimen.
The combination of raltegravir, ETR, and DRV/r was a highly effective and well-tolerated antiretroviral salvage regimen in patients infected with multidrug-resistant HIV-1.
在DUET试验中，增强型达芦那韦（DRV/r）联合依曲韦林（ETR），以及在BENCHMRK试验中，拉替拉韦，在多重耐药HIV-1感染患者中显示出高病毒学应答率，特别是与另外两种活性更完全的抗逆转录病毒药物联合使用时。尚无关于这种联合用药的临床试验数据。
对32例连续的多重耐药HIV-1感染且接受过大量治疗的患者进行研究，这些患者开始使用拉替拉韦（RAL，每日两次，每次400mg）、依曲韦林（ETR，每日两次，每次200mg）和增强型达芦那韦（DRV/r，每日两次，每次600/100mg）进行新的挽救治疗方案。在基线以及第4、12和24周收集临床评估以及免疫、病毒学和生化参数。
基线特征中位数为年龄44岁，接受抗逆转录病毒治疗13年，之前接受过9种高效抗逆转录病毒治疗方案，CD4细胞计数为261个/mL，HIV-1 RNA为4.2 log10拷贝/mL。分别有16例（50%）和14例（44%）患者曾使用过恩夫韦肽和替拉那韦。所有患者均存在三类耐药突变。3例患者（9%）的病毒分离株带有三种依曲韦林耐药突变。所有患者均未使用过达芦那韦，耐药突变中位数为一种达芦那韦耐药突变。在第4、12和24周时，分别有63%、81%和94%的患者HIV-1 RNA水平低于50拷贝/mL。CD4细胞计数中位数在第4、12和24周时分别增加了30、73和103个/mL。没有患者出现导致治疗方案中断的不良事件。
对于多重耐药HIV-1感染患者，拉替拉韦、依曲韦林和增强型达芦那韦联合使用是一种高效且耐受性良好的抗逆转录病毒挽救治疗方案。
