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
- 52
- 试验地点
- 1
- 主要终点
- Cav of TFV-DP and FTC-TP PK in HIV-infected adolescents with and without TB coinfection.
研究概览
简要总结
Tenofovir (TFV) disoproxil fumarate (TDF) plus emtricitabine (FTC) or lamivudine (3TC) is the preferred nucleoside backbone of first-line antiretroviral therapy (ART) for adolescents in sub-Saharan Africa. In addition, TDF/FTC is recommended for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection in adolescents at substantial risk of acquisition of HIV infection, as well as for hepatitis B virus (HBV) treatment in those with HBV/HIV coinfection. The efficacy TDF and FTC are dependent on intracellular concentrations of the active phosphate anabolites, called TFV diphosphate (TFV-DP) and FTC triphosphate (FTC-TP). However, the intracellular pharmacokinetics of TFV-DP and FTC-TP to examine the adequacy of current dosages in African adolescents has not been previously studied. Thus, examining the pharmacokinetics (PK) of these widely used antiretrovirals in African adolescents is important as ART outcomes remain poor and the recommended dosages of these drugs for children and adolescent were extrapolated from drug approval clinical trials in adult in the United States and Europe.
详细描述
This study will evaluate the intracellular PK of TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents with and without TB coinfection. As the clinical effects of TDF and FTC are related to the intracellular concentrations of the phosphate anabolites, called TFV-DP and FTC-TP, there is a need to understand the cellular pharmacology of TDF interactions in African HIV-infected adolescents with and without TB, as the study team cannot extrapolate from US patients not on antituberculosis (anti-TB) drugs. This study will enroll HIV-infected adolescents aged 10 to 18 years old with and without TB coinfection who are already established on ART. The study team hypothesize that younger age, adenosine triphosphate (ATP)-binding cassette subfamily C (ABCC) single nucleotide polymorphisms (SNPs) and anti-TB therapy may influence the intracellular TFV-DP and FTC-TP concentrations in adolescents.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 10 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-infected adolescents aged 10 to 19 years old who are stable on antiretroviral regimen containing TDF/FTC (300/200 mg daily) for at least 8 weeks.
排除标准
- •Unable to obtain informed signed consent from parent(s) or legal guardian.
- •Pregnant or breast feeding.
- •Require therapy for other opportunistic infections other than tuberculosis (TB).
结局指标
主要结局
Cav of TFV-DP and FTC-TP PK in HIV-infected adolescents with and without TB coinfection.
时间窗: After at least 8 weeks of HIV therapy.
Geometric mean intracellular TFV-DP and FTC-TP Cav in adolescents with TB/HIV coinfection compared to those only HIV infection.
AUC0-24h of TFV-DP and FTC-TP PK in HIV-infected adolescents with and without TB coinfection.
时间窗: After at least 8 weeks of HIV therapy.
Geometric mean of intracellular TFV-DP and FTC-TP AUC0-24h in adolescents with TB/HIV coinfection compared to those with only HIV infection.
Average concentration (Cav) of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.
时间窗: After at least 8 weeks of HIV therapy.
Mean and median Cav of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.
Area under the time-concentration curve 0-24 hours (AUC0-24h) of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.
时间窗: After at least 8 weeks of HIV therapy.
Mean and median AUC0-24h of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.
次要结局
- Effect of age on TFV-DP and FTC-TP Cav.(After at least 8 weeks of HIV therapy.)
- Intracellular TFV-DP and FTC-TP AUC0-24h in adolescents compared to that in historical adult controls.(After at least 8 weeks of HIV therapy.)
- Effect of age on TFV-DP and FTC-TP AUC0-24h .(After at least 8 weeks of HIV therapy.)
- Prevalence and covariates of intracellular TFV-DP Cav < 95 fmol/106 cells in adolescents.(After at least 8 weeks of HIV therapy.)
- Intracellular TFV-DP and FTC-TP Cav in adolescents compared to that in historical adult controls.(After at least 8 weeks of HIV therapy.)
- Relationship between Adenosine triphosphate (ATP)-binding cassette subfamily C, member 2 (ABCC2), member 4 (ABCC4) and member 10 (ABCC10) SNPs and TFV-DP and FTC-TP AUC0-24h.(After at least 8 weeks of HIV therapy.)