Maintenance of Switching From Protease Inhibitor/Ritonavir to Generic Single Tablet Regimen of Tenofovir Alafenamide/Emtricitibine/Dolutegravir in Virologically Suppressed HIV-infected Adults
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 170
- 试验地点
- 2
- 主要终点
- number of subjects with undetectable viral load
研究概览
简要总结
This is a phase III, multicenter, open-label, single-arm study of 190 virologically suppressed HIV-infected adults
详细描述
The fundamental principle of regimen switching is to maintain viral suppression without jeopardizing future treatment options. The reasons to consider regimen switching in the viral suppressed population are to simplify the regimen by reducing the pill burden and dosing frequency, to increase the tolerability, reduce the adverse effects as well as long-term toxicities, to prevent drug-to-drug interactions and to avoid the dietary requirements.
Generic TAF/E/D (tenofovir alafenamide 25mg/emtricitabine 200mg/dolutegravir 50 mg), a single-tablet once daily regimen, will be an affordable regimen with the potential characteristics such as reduced pill burden, less drug to drug interaction and toxicities. The generic form (Mylan) is recently received the tentative approval from the U.S. Food and Drug Administration (FDA) under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Whether DTG-containing regimen is a better option than protease inhibitors among resource-limited settings during the decisions for second-line treatment options, is needed to be evaluated.
All participants will be switched from their pre-study ART regimen to a single tablet regimen (STR) of TAF/FTC/DTG 25/200/50mg once daily.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented HIV-1 infection
- •Aged ≥18 years old
- •Female participant may be eligible to participate if she:
- •is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea or >=54 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, is of child-bearing potential, with a negative pregnancy test at both Screening and week 0 and agrees to use one of the protocol-defined methods of contraception to avoid pregnancy.
- •On current ART for at least 6 months prior to study entry
- •Current ART includes boosted protease inhibitors
- •No more than one HIV-1 plasma RNA >50 copies/mL and <200 copies/L (only one 'blip') in the past 6 months with a subsequent HIV-1 plasma RNA <50 copies/mL
- •HIV-1 plasma RNA <50 copies/mL at screening visit
- •No prior or current exposure to integrase strand transfer inhibitor (INSTI)
- •Have signed the informed consent form
排除标准
- •Breastfeeding female
- •Pregnancy or positive UPT at screening
- •Calculated creatinine clearance as estimated by Cockcroft-Gault equation (CrCl) <60 mL/min,
- •Alanine aminotransferase (ALT) >2.5 x ULN,
- •Concomitant use of any of the following medications:
- •(1) aluminum and magnesium-containing antacids, proton-pump inhibitors (2) anticonvulsants: carbamazepine, oxcarbamazepine, phenobarbital, phenytoin (3) antimycobacterials: rifabutin, rifampin, rifapentine (4) St. John's wort
- •Alcohol or drug abuse that, in the opinion of the investigator, would interfere with completion of study procedures
- •Any serious illness that, in the opinion of the investigator, would interfere with completion of study procedures
研究组 & 干预措施
generic single tablet regimen of tenofovir alafenamide/e
HIV infected adults currently on protease inhibitor/ritonavir will switch to use generic single tablet regimen of tenofovir alafenamide/emtricitibine/dolutegravir to see if the single tablet can continue to suppress viral replication and be used as a maintenance regimen
干预措施: generic single tablet TAF/FTC/DTG (Drug)
结局指标
主要结局
number of subjects with undetectable viral load
时间窗: 48 weeks
Proportion of participants with plasma HIV-1 RNA \<50 copies/mL using Snapshot algorithm at week 48
次要结局
- Cmax of DTG(weeks 24 and weeks 48)
- T1/2 of DTG(weeks 24 and weeks 48)
- CL of DTG(weeks 24 and weeks 48)
- Changes from baseline in fasting lipid profiles(weeks 24 and weeks 48)
- Changes from baseline in insulin(weeks 24 and weeks 48)
- Proportion of participants without tolerability failure(weeks 24 and weeks 48)
- Tmax of DTG(weeks 24 and weeks 48)
- AUC of DTG(weeks 24 and weeks 48)
- Changes from baseline in renal parameters (creatinine, eGFR)(weeks 24 and weeks 48)
- Changes from baseline in transient elastography results(weeks 24 and weeks 48)
- Ke of DTG(weeks 24 and weeks 48)
- Anxiety at baseline will be compared to level of anxiety at weeks 24 and weeks 48.(weeks 24 and weeks 48)
- Depression at baseline will be compared to depression level at weeks 24 and weeks 48.(weeks 24 and weeks 48)
- Changes from baseline in fasting blood glucose levels(weeks 24 and weeks 48)