Pharmacokinetics and Efficacy of Low- or Standard-dose of Lopinavir/Ritonavir (Kaletra®) in PI-naïve HIV-1 Infected Children
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- pharmacokinetics of standard vs low dose LPV/r
研究概览
简要总结
To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in ARV PI naive HIV-1 infected Thai children.
To study clinical and immunological efficacy after 48 weeks of lopinavir/ritonavir in PI naïve HIV-1 infected Thai children
详细描述
In 2002, the Thai Ministry of Public Health (MOPH) launched the National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA) with the aim of providing treatment to all Thai patients who needed antiretroviral treatment. By the end of 2005, 80,000 HIV-infected Thais were treated in the NAPHA program, including about 6,000 children. The antiretroviral treatment regimen consists of three antiretroviral drugs (ARV). The first-line regimen used in NAPHA are mainly generic drugs produced by Thai government pharmaceutical organization (GPO), including a fixed-drug combination of stavudine, lamivudine, and nevirapine (GPOvir);and a fixed-drug combination of zidovudine, lamivudine, and nevirapine (GPOvir-Z). Majority of patients respond very well with first-line regimen(1,2), however about 15% of patients have drug resistance to first-line regimen and require second-line regimen(3). The protease inhibitors (PIs) is used as a second-line regimen, however there are limitations in terms of cost and metabolic complications(4).
Lopinavir/ritonavir is the most widely use protease inhibitors in children because of its high efficacy and a syrup formulation that easy to use in small children. There is evidence supported that the recommended dose according to US-FDA or EU guidelines resulting in much higher plasma blood level in Thai children. Data from 19 Thai children demonstrated Cmin of 5.9 mg/L compare to 3.4 mg/L in US children when use the same dose (the minimum acceptable Cmin is 1.0 mg/L) (5,6). There is a study HIVNAT019, which demonstrated acceptable LPV plasma concentration and treatment outcome in Thai HIV-infected adult when use reduced dose of LPV/r 266mg/66 mg compare to standard dose of 400mg/100mg (7).
Therefore, the study of pharmacokinetic of low dose of LPV/r in Thai HIV-infected children is very important to assess the safety and efficacy of this strategy. This will lead to appropriate ARV dose in children to reduce long-term adverse events, and also reduce the ARV cost.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age from 2- 18 years old
- •Documented positive test for HIV-1 infection
- •HIV RNA viral load > 1,000 copies
- •Written informed consent
排除标准
- •Active opportunistic infection
- •Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
- •Use of concomitant medication that may interfere with the pharmacokinetics of lopinavir/ritonavir
- •Pregnancy or lactating
- •Inability to understand the nature and extent of the study and the procedures required.
研究组 & 干预措施
1
Lopinavir/ritonavir standard dose + zidovudine and lamivudine
干预措施: Lopinavir/ritonavir standard dose According to WHO simplified dosing table (Drug)
2
Lopinavir/ritonavir low dose (70% of standard dose) + zidovudine and lamivudine
干预措施: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table) (Drug)
结局指标
主要结局
pharmacokinetics of standard vs low dose LPV/r
时间窗: 4 weeks after start ART
次要结局
- efficacy and safety of standard and low dose LPV/r(48 weeks)