Blood Levels of Anti-HIV Drugs Used in Combination Regimens in HIV Infected Children

November 3, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Intensive Pharmacokinetic Studies of Antiretroviral Drug Combinations in Children

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • San Juan City Hosp. PR NICHD CRS
      • San Juan, Puerto Rico, 00935
        • University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
  • United States
    • California
      • Alhambra, California, United States, 91803
        • Usc La Nichd Crs
      • La Jolla, California, United States, 92093-0672
        • University of California, UC San Diego CRS
      • Long Beach, California, United States, 90806
        • Miller Children's Hosp. Long Beach CA NICHD CRS
      • Torrance, California, United States, 90502
        • Harbor UCLA Medical Ctr. NICHD CRS
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Med. Ctr.
    • Florida
      • Miami, Florida, United States, 33136
        • Pediatric Perinatal HIV Clinical Trials Unit CRS
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Univ. Cook County Hosp. Chicago NICHD CRS
      • Chicago, Illinois, United States, 60614-3393
        • Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Univ. of Maryland Baltimore NICHD CRS
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Univ. Baltimore NICHD CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hosp. of Boston NICHD CRS
      • Springfield, Massachusetts, United States, 01199
        • Baystate Health, Baystate Med. Ctr.
      • Worcester, Massachusetts, United States, 01605
        • WNE Maternal Pediatric Adolescent AIDS CRS
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan NICHD CRS
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers - New Jersey Medical School CRS
    • New York
      • Bronx, New York, United States, 10461
        • Jacobi Med. Ctr. Bronx NICHD CRS
      • Brooklyn, New York, United States, 11203
        • SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
      • New York, New York, United States, 10016
        • Nyu Ny Nichd Crs
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • DUMC Ped. CRS
    • Tennessee
      • Memphis, Tennessee, United States, 38105-3678
        • St. Jude Children's Research Hospital CRS
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: D
TDF and EFV or NVP throughout study
Drug: Efavirenz
Dosage dependent on participant
Other Names:
  • EFV
Drug: Nevirapine
Dosage dependent on participant
Other Names:
  • NVP
Drug: Tenofovir disoproxil fumarate
300 mg orally daily
Other Names:
  • TDF
Procedure: Pharmacokinetic Study
Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Other Names:
  • PK Study
Experimental: E
TDF and DRV with or without EFV throughout study
Drug: Efavirenz
Dosage dependent on participant
Other Names:
  • EFV
Drug: Tenofovir disoproxil fumarate
300 mg orally daily
Other Names:
  • TDF
Procedure: Pharmacokinetic Study
Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Other Names:
  • PK Study
Drug: Darunavir
300 mg or 600 mg orally twice daily
Other Names:
  • DRV
Drug: Ritonavir
50 mg or 100 mg orally twice daily
Other Names:
  • RTV
Experimental: F
TDF and ATV and RTV with or without EFV throughout study
Drug: Efavirenz
Dosage dependent on participant
Other Names:
  • EFV
Drug: Tenofovir disoproxil fumarate
300 mg orally daily
Other Names:
  • TDF
Procedure: Pharmacokinetic Study
Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Other Names:
  • PK Study
Drug: Ritonavir
50 mg or 100 mg orally twice daily
Other Names:
  • RTV
Drug: Atazanavir
200 mg to 400 mg orally daily
Other Names:
  • ATV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC)
Time Frame: Over the dosing interval
Over the dosing interval

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Study Chair: Jennifer King, PharmD, Department of Pharmacology and Toxicology, University of Alabama at Birmingham
  • Study Chair: Ram Yogev, MD, Section of Pediatrics and Maternal HIV Infection, Children's Memorial Hospital, Northwestern University Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

November 29, 2005

First Submitted That Met QC Criteria

November 29, 2005

First Posted (Estimate)

December 1, 2005

Study Record Updates

Last Update Posted (Actual)

November 9, 2021

Last Update Submitted That Met QC Criteria

November 3, 2021

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P1058
  • 10050 (Registry Identifier: DAIDS-ES)
  • PACTG 1058
  • IMPAACT P1058

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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