Blood Levels of Anti-HIV Drugs Used in Combination Regimens in HIV Infected Children
- Conditions
- HIV Infections
- Interventions
- Procedure: Pharmacokinetic Study
- Registration Number
- NCT00260078
- Brief Summary
Limited data exist about combination anti-HIV treatment regimens in children, including how those drugs are cleared by the body in children. The purpose of this study is to measure the blood levels of the following combinations of anti-HIV drugs in HIV infected chilren: tenofovir disoproxil fumurate (TDF) and efavirenz (EFV) or nevirapine (NVP); TDF and darunavir (DRV) with or without EFV; and TDF and ritonavir (RTV) with or without EFV.
- Detailed Description
Because all of the available non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) are metabolized by and affect hepatic cytochrome enzymes, combinations of two or more of these drugs produce complex pharmacokinetic (PK) interactions. However, little data exist regarding PK of anti-HIV drug combinations in the pediatric population. The purpose of this study is to assess steady-state PK of the following anti-HIV regimens: TDF and EFV or NVP; TDF and DRV with or without EFV; and TDF and RTV with or without EFV. In addition, this study will evaluate how age, length of treatment, adverse effects, and genes affect children's response to different anti-HIV combinations.
This study will last between 1 and 7 weeks. Participants in this study will be grouped based on the treatment regimen they are receiving or about to initiate. There are three groups in this study. Group D participants will receive TDF and EFV or NVP; Group E participants will receive TDF and DRV with or without EFV; and Group F participants will receive TDF and RTV with or without EFV. The inclusion of EFV or NVP will be dependent on each participant's prescribed regimen. Participants within each group will be stratified by age and how long they have been receiving their anti-HIV regimens. Antiretrovirals will not be provided by this study.
Most participants will have two study visits. The first visit will occur at study entry. Medical history, a physical exam, and blood collection will occur. The second visit will occur within 35 days of study entry and will take approximately 24 hours. Blood collection for PK studies, a physical exam, and medical history will be done at this visit. Urine collection will occur at all visits for female participants.
Participants will undergo PK testing at least 14 days after initiating their study regimens. Participants will be given a dose of their anti-HIV medications with food. A blood sample will be taken before dosing. Blood samples will also be taken at 1, 2, 4, 6, 8, 12, and 24 hours after dosing. Participants in Groups E and F may need to repeat PK testing within 6 weeks of initial PK testing at the discretion of the investigator.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
- HIV infected
- Currently receiving or about to initiate one of the following anti-HIV regimens: TDF with EFV or NVP, TDF and DRV/r with or without EFV, or TDF with ATV/r with or without EFV
- Body surface area at least 0.85 m2
- Parent or guardian willing and able to provide signed informed consent
- Willing to use acceptable forms of contraception
- Liver disease that may affect the metabolism of study drugs
- Certain abnormal laboratory values
- Require certain medications
- Treatment with any anti-HIV or nonantiretroviral drug that could interact with drugs under PK study in the 14 days prior to study entry
- Any clinical or laboratory toxicity of Grade 4 or higher at screening. More information on this criterion can be found in the protocol.
- Pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description D Pharmacokinetic Study TDF and EFV or NVP throughout study E Pharmacokinetic Study TDF and DRV with or without EFV throughout study F Pharmacokinetic Study TDF and ATV and RTV with or without EFV throughout study E Ritonavir TDF and DRV with or without EFV throughout study E Tenofovir disoproxil fumarate TDF and DRV with or without EFV throughout study D Nevirapine TDF and EFV or NVP throughout study D Efavirenz TDF and EFV or NVP throughout study D Tenofovir disoproxil fumarate TDF and EFV or NVP throughout study E Darunavir TDF and DRV with or without EFV throughout study E Efavirenz TDF and DRV with or without EFV throughout study F Efavirenz TDF and ATV and RTV with or without EFV throughout study F Atazanavir TDF and ATV and RTV with or without EFV throughout study F Ritonavir TDF and ATV and RTV with or without EFV throughout study F Tenofovir disoproxil fumarate TDF and ATV and RTV with or without EFV throughout study
- Primary Outcome Measures
Name Time Method Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC) Over the dosing interval
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (23)
Rush Univ. Cook County Hosp. Chicago NICHD CRS
🇺🇸Chicago, Illinois, United States
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
🇺🇸Chicago, Illinois, United States
Children's Hosp. of Boston NICHD CRS
🇺🇸Boston, Massachusetts, United States
Seattle Children's Hospital CRS
🇺🇸Seattle, Washington, United States
DUMC Ped. CRS
🇺🇸Durham, North Carolina, United States
Usc La Nichd Crs
🇺🇸Alhambra, California, United States
University of California, UC San Diego CRS
🇺🇸La Jolla, California, United States
Harbor UCLA Medical Ctr. NICHD CRS
🇺🇸Torrance, California, United States
Miller Children's Hosp. Long Beach CA NICHD CRS
🇺🇸Long Beach, California, United States
Connecticut Children's Med. Ctr.
🇺🇸Hartford, Connecticut, United States
Pediatric Perinatal HIV Clinical Trials Unit CRS
🇺🇸Miami, Florida, United States
Univ. of Maryland Baltimore NICHD CRS
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Univ. Baltimore NICHD CRS
🇺🇸Baltimore, Maryland, United States
Baystate Health, Baystate Med. Ctr.
🇺🇸Springfield, Massachusetts, United States
Children's Hospital of Michigan NICHD CRS
🇺🇸Detroit, Michigan, United States
Rutgers - New Jersey Medical School CRS
🇺🇸Newark, New Jersey, United States
SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
🇺🇸Brooklyn, New York, United States
Jacobi Med. Ctr. Bronx NICHD CRS
🇺🇸Bronx, New York, United States
Nyu Ny Nichd Crs
🇺🇸New York, New York, United States
St. Jude Children's Research Hospital CRS
🇺🇸Memphis, Tennessee, United States
San Juan City Hosp. PR NICHD CRS
🇵🇷San Juan, Puerto Rico
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
🇵🇷San Juan, Puerto Rico
WNE Maternal Pediatric Adolescent AIDS CRS
🇺🇸Worcester, Massachusetts, United States