Harris Marianne, Ganase Bruce, Watson Birgit, Harrigan P Richard, Montaner Julio S G, Hull Mark W
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
AIDS Research Program, St. Paul's Hospital, Vancouver, BC, Canada.
AIDS Res Ther. 2017 Nov 2;14(1):59. doi: 10.1186/s12981-017-0185-4.
As a simplification strategy for treatment-experienced HIV-infected patients who have achieved virologic suppression on a multi-drug, multi-class antiretroviral regimen, the aim of this study was to evaluate the safety, efficacy, and pharmacokinetics of once-daily elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) with darunavir.
A single arm, open-label 48-week study was conducted of regimen simplification to E/C/F/TDF plus darunavir 800 mg daily from stable therapy including two nucleoside/nucleotide reverse transcriptase inhibitors, a ritonavir-boosted protease inhibitor, and an integrase inhibitor. Participants had plasma HIV viral load consistently < 200 copies/mL for ≥ 6 months, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, and no genotypic resistance to major components of the study regimen. Plasma viral load was measured at weeks 2 and 4, then every 4 weeks throughout the study. Safety laboratory assessments were conducted at baseline and at weeks 12, 24, 36, and 48. Antiretroviral drug concentrations were measured at baseline and once ≥ 2 weeks after the regimen change.
Ten HIV-infected adults (8 male and 2 female; median age 50.5 years) were enrolled. All maintained virologic suppression on the new regimen for 48 weeks. One subject experienced a decrease in eGFR from 62 mL/min at baseline to 52 mL/min at week 12; study medications were continued and his eGFR remained stable (50-59 mL/min) thereafter. No subjects discontinued study medications for renal function changes or other adverse events. Darunavir trough concentration were lower on the new regimen than on darunavir/ritonavir 800/100 mg (n = 5; p < 0.05).
Despite low darunavir trough concentrations, treatment simplification to a two-pill, once-daily regimen of E/C/F/TDF plus darunavir was safe and effective for 48 weeks among 10 selected treatment-experienced HIV-infected patients. Trial registration The study protocol was registered with ClinicalTrials.gov (NCT02199613) on July 22, 2014.
作为对在多药、多类别抗逆转录病毒治疗方案中实现病毒学抑制的有治疗经验的HIV感染患者的一种简化治疗策略，本研究旨在评估每日一次的埃替拉韦/考比司他/恩曲他滨/替诺福韦酯（E/C/F/TDF）联合达芦那韦的安全性、有效性和药代动力学。
开展了一项单臂、开放标签的48周研究，旨在将治疗方案简化为E/C/F/TDF加每日800毫克达芦那韦，治疗对象为正在接受包括两种核苷/核苷酸逆转录酶抑制剂、一种利托那韦增强的蛋白酶抑制剂及一种整合酶抑制剂的稳定治疗的患者。参与者的血浆HIV病毒载量持续<200拷贝/毫升达≥6个月，估计肾小球滤过率（eGFR）≥60毫升/分钟，且对研究方案的主要成分无基因型耐药。在第2周和第4周测量血浆病毒载量，然后在整个研究过程中每4周测量一次。在基线以及第12周、24周、36周和48周进行安全性实验室评估。在基线以及治疗方案改变后≥2周时测量抗逆转录病毒药物浓度。
招募了10名HIV感染的成年人（8名男性和2名女性；中位年龄50.5岁）。所有人在新方案上维持病毒学抑制达48周。一名受试者的eGFR从基线时的62毫升/分钟降至第12周时的52毫升/分钟；继续使用研究药物，此后其eGFR保持稳定（50 - 59毫升/分钟）。没有受试者因肾功能变化或其他不良事件而停用研究药物。新方案下达芦那韦谷浓度低于达芦那韦/利托那韦800/100毫克方案（n = 5；p < 0.05）。
尽管达芦那韦谷浓度较低，但对于10名选定的有治疗经验的HIV感染患者，简化为每日一次服用两片的E/C/F/TDF联合达芦那韦方案在48周内是安全有效的。试验注册 本研究方案于2014年7月22日在ClinicalTrials.gov（NCT02199613）注册。
