A Comparison of Two Anti-HIV Drug Regimens for Youth Who Have Failed Prior Therapy

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00102206
First received: January 25, 2005
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

HIV infected children and adolescents who have taken many anti-HIV drugs may have limited treatment options and are at high risk for progressing to AIDS. The purpose of this study is to determine whether an anti-HIV treatment regimen of 2 protease inhibitors (PIs) and 2 nucleoside reverse transcriptase inhibitors (NRTIs) is more effective than a regimen of 4 NRTIs in treatment-experienced children and adolescents who have failed previous anti-HIV treatment.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate
Drug: Emtricitabine
Drug: Lamivudine
Drug: Lopinavir/ritonavir
Drug: Saquinavir
Drug: Tenofovir disoproxil fumarate
Drug: Zidovudine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Open-Label Study to Evaluate the Safety and Effectiveness of Two Antiretroviral Therapeutic Strategies: A Dual PI-Based HAART Regimen Versus a Multi-NRTI ART Regimen, in ART-Experienced Children and Youth Who Have Experienced Virologic Failure

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Tolerability of dual PI-based HAART versus multi-NRTI HAART salvage regimens (time to first intolerant event)
  • 95% confidence interval (CI) for change in CD4% computed for PI-containing groups versus PI-sparing group
  • 95% CI for change in BMD (both percent change in BMD and change in z-score from baseline) for each treatment group

Secondary Outcome Measures:
  • HIV-1 RNA
  • growth and development markers
  • toxicity
  • adherence
  • pharmacokinetics
  • special virologic and immunologic parameters

Enrollment: 6
Study Completion Date: May 2007
Detailed Description:

HIV infected children and adolescents on anti-HIV treatment regimens have traditionally had more difficulty with non-adherence and drug resistance than adults, often resulting in virologic failure. Additionally, HIV infected children with extensive exposure to antiretrovirals (ARVs) are likely to have fewer therapeutic options for salvage therapy, and their physicians find it difficult to choose regimens that will keep the HIV infection under control. This study will compare the efficacy of three 4-drug ARV salvage regimens in treatment-experienced, HIV infected children and adolescents who have experienced virologic failure.

This study will last at least 96 weeks. Participants will be randomly assigned to one of three groups. Group 1A will receive a dual-PI based regimen of lopinavir/ritonavir (LPV/r), saquinavir (SQV), and the NRTIs emtricitabine (FTC) and abacavir sulfate (ABC). Group 1B will receive a dual-PI based regimen of LPV/r, SQV, FTC, and tenofovir disoproxil fumarate (TDF). Group 2 will receive an NRTI-only regimen of ABC, lamivudine, zidovudine, and TDF.

There will be 11 study visits during Step I of this study. Medical history, a physical exam, and blood collection will occur at all visits. Dual-energy x-ray absorptiometry (DEXA) scans will occur at study entry and at Weeks 24, 48, 72, and 96. Urine collection will occur at most visits; participants will also take part in adherence modules at most visits. Participants will be asked to complete a pill count form at Weeks 4 and 24. Additionally, some study participants will be asked to participate in an intensive pharmacokinetics study at Week 4.

  Eligibility

Ages Eligible for Study:   4 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Step I:

  • HIV infected
  • No currently available therapeutic options that would likely result in long-term suppression of virus to less than 400 copies/ml
  • Two measurements within 4 months prior to screening and at screening of either CD4% of less than 15% and HIV viral load of greater than 10,000 copies/ml OR HIV viral load greater than 30,000 copies/ml
  • Previous exposure to non-nucleoside reverse transcriptase inhibitors (NNRTIs), NRTIs, and PIs AND have experienced virologic failure. More information on previous treatment regimen requirements is available in the protocol.
  • Prior or current virologic failure with genotypic or phenotypic resistance OR historical virologic failure with a PI- or NNRTI-containing regimen
  • Resistance to 2 or more drugs in most recent treatment regimen within 26 weeks prior to study screening
  • Able and willing to swallow study medications
  • Parent or guardian willing to provide informed consent, if applicable
  • Willing to use acceptable methods of contraception

Exclusion Criteria for Step I:

  • Previous cumulative exposure to TDF for more than 24 weeks OR more than 14 days of TDF exposure during the 24 weeks prior to study entry
  • Grade 1 lipase or higher within 28 days prior to study entry
  • Grade 3 or higher laboratory abnormality (except for lipase) within 28 days prior to study entry
  • History of allergy or hypersensitivity to any of the study drugs
  • Active CDC Stage C opportunistic infection or serious bacterial infection requiring therapy at the time of screening
  • Chemotherapy for active cancer
  • Require certain medications
  • Abnormal kidney function
  • Any clinically significant diseases other than HIV infection or findings during medical history screening that, in the opinion of the investigator, may interfere with the study
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00102206

Locations
United States, Illinois
Chicago Children's CRS
Chicago, Illinois, United States, 60614
United States, New York
Columbia IMPAACT CRS
New York, New York, United States
SUNY Stony Brook NICHD CRS
Stony Brook, New York, United States, 11794-8111
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Investigators
Study Chair: Andrew Wiznia, MD Jacobi Medical Center
Study Chair: Ann J. Melvin, MD, MPH Seattle Children's Hospital and Regional Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00102206     History of Changes
Other Study ID Numbers: P1053, 10131, PACTG P1053
Study First Received: January 25, 2005
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced
Child

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Abacavir
Emtricitabine
Lopinavir
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014