HIV Infections
Conditions
Keywords
Treatment Experienced, Pharmacokinetics, PK
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.
Interventions
DRUGAtazanavir
200 mg to 400 mg orally daily
DRUGDarunavir
300 mg or 600 mg orally twice daily
DRUGEfavirenz
Dosage dependent on participant
DRUGNevirapine
Dosage dependent on participant
DRUGRitonavir
50 mg or 100 mg orally twice daily
DRUGTenofovir disoproxil fumarate
300 mg orally daily
PROCEDUREPharmacokinetic Study
Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Note: The original Groups A, B, and C have been removed, and Groups D, E, and F have been added per protocol amendment dated 11/16/07. Inclusion Criteria: * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC) | Over the dosing interval |
Countries
Puerto Rico, United States
Outcome results
None listed