Blood Levels of Anti-HIV Drugs Used in Combination Regimens in HIV Infected Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Atazanavir; Darunavir; Efavirenz; Nevirapine; Ritonavir; Tenofovir disoproxil fumarate; Pharmacokinetic Study
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Procedure
Intervention description(s): 200 mg to 400 mg orally daily; 300 mg or 600 mg orally twice daily; Dosage dependent on participant; Dosage dependent on participant; 50 mg or 100 mg orally twice daily; 300 mg orally daily; Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Other intervention name(s): ATV; DRV; EFV; NVP; RTV; TDF; PK Study
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate; Darunavir; Tenofovir; Nevirapine; Efavirenz
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Treatment Experienced; Pharmacokinetics; PK