Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 213
- 试验地点
- 1
- 主要终点
- TB coinfection status and HIV RNA < 200 copies/mL on EFV-based ART in HIV-infected children.
研究概览
简要总结
Efavirenz (EFV)-based antiretroviral therapy (ART) remains the preferred regimen in human immunodeficiency virus (HIV)-infected children aged 3 years or older on rifampin-containing antituberculosis (anti-TB) therapy. This is because drug interactions between first-line anti-TB therapy with protease inhibitors (PIs) are more severe to adjust for, and interactions with integrase strand transfer inhibitors (INSTIs) are not well studied in that age group. Although, current weight-based EFV dosing recommendation is not optimal in some children, pharmacokinetic-treatment response (PK-PD) data to guide optimal dosing of EFV during concurrent rifampin-containing therapy in children is very limited. The study team propose that EFV concentrations outside the optimal therapeutic range in children will be associated with virologic failure due to lack of efficacy because of low concentrations or increased central nervous system (CNS) toxicities from high concentrations leading to poor medication adherence. The study will determine virological suppression rates in HIV-infected children with and without TB coinfection treated with standard efavirenz-based therapy and examine the factors contributing to poor virologic response.
详细描述
In a previous study, the study team found that first-line anti-TB therapy had minimal effect on EFV pharmacokinetics (PK) at the population level, but children with TB/HIV coinfection on anti-TB therapy had a trend towards worse virologic outcome compared to those with only HIV infection. Due to the small sample size, the study team were unable to examined the patient factors contributing to the poor virologic response. The study team hypothesized that virologic suppression rates on EFV-based therapy is significantly lower in children with TB/HIV coinfection compared to those with HIV alone. In addition, virologic response will be dependent EFV plasma concentrations, CYP2B6 516 G>T genotype and/or adherence level. This hypothesis is based on the premise that extremes (low and high EFV concentration, respectively) could lead to virologic failure because of lack of efficacy or intolerable side effects leading to poor adherence. The current study will investigate the effect of anti-TB therapy, CYP2B6 genotype and pharmacokinetically determined adherence level on virologic response in children with TB/HIV coinfection treated with EFV-based ART.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 3 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV seropositive children with or without active TB
- •Antiretroviral-naïve to efavirenz and meet criteria for initiation or switch to efavirenz-based ART
- •Are available for follow-up until achievement of a study endpoint like completion of study at 6 months or discontinuation of ART.
排除标准
- •Unable to obtain informed signed consent parent(s) or legal guardian
- •Have AIDS-related opportunistic infections other than TB
- •History of acute hepatitis within 30 days of study entry
- •Persistent vomiting or diarrhea at time of enrolment
- •Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) > 2 times upper limit of normal
结局指标
主要结局
TB coinfection status and HIV RNA < 200 copies/mL on EFV-based ART in HIV-infected children.
时间窗: At week 24 of HIV therapy.
The proportion of children with TB/HIV coinfection with virological suppression (HIV RNA \< 200 copies/mL) on EFV-based ART and anti-TB therapy compared to that in children with only HIV infection on EFV-based therapy.
次要结局
- CYP2B6 516G>T genotype status and HIV RNA suppression < 200 copies/mL.(Up to week 24 of HIV therapy.)
- TB coinfection status and risk of virological failure on EFV-based ART.(Up to week 48 of HIV therapy.)
- Random efavirenz concentration below the limit of detection (poor ART adherence) and HIV RNA suppression rate.(Up to week 24 of HIV therapy.)
- CYP2B6 516G>T genotype status and random efavirenz concentration below the limit of detection (poor ART adherence).(Up to week 24 of HIV therapy.)
- Efavirenz plasma mid-dose concentration and HIV RNA suppression < 200 copies/mL.(Up to week 24 of HIV therapy.)