A Study to Compare Two Different Anti-HIV Drug Regimens

A Phase II Randomized, Multicenter Protocol Evaluating Two Antiretroviral Regimens Containing Combinations of Protease Inhibitors, NRTIs, and an NNRTI

This study compares 2 different anti-HIV drug regimens to determine which is the most effective in lowering the amount of HIV in the blood. The anti-HIV drugs used in this study are 2 protease inhibitors (nelfinavir and ritonavir), 2 nucleoside reverse transcriptase inhibitors (stavudine and didanosine), and 1 nonnucleoside reverse transcriptase inhibitor (nevirapine).

These drug combinations have been previously studied in adults, but there is limited information on how well they work in HIV-infected children. It is important to develop drug combinations which are effective at suppressing the HIV virus in children.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine; Drug: Stavudine; Drug: Ritonavir; Drug: Didanosine; Drug: Nelfinavir mesylate

Detailed Description

The use of combination therapy with 2 or more antiretroviral agents has been strongly supported by recent studies in both children and adults. However, as of yet, few combinations of antiretrovirals have been studied in large cohorts of stable HIV-1 infected, antiretroviral-experienced children. Evidence suggests that viral suppression may be more difficult to achieve in children. Therefore, it is important to develop new drug combinations which can maximally suppress plasma HIV-1 RNA concentrations in children.

Patients are stratified by prior antiretroviral treatment (zidovudine [ZDV]/lamivudine [3TC] versus d4T/other treatment) and by age (under 24 months versus 24 months and older). Patients are then randomized to 1 of 4 treatment groups.

Arm A1: ddI/NFV/RTV (for prior ZDV/3TC-treated patients). Arm A2: ddI/NFV/RTV (for prior d4T/other-treated patients). Arm B1: d4T/NFV/NVP (for prior ZDV/3TC-treated patients). Arm B2: d4T/NFV/NVP (for prior d4T/other-treated patients). Treatment is administered for 48 weeks. At Weeks 2, 4, and then every 4 weeks thereafter, patients undergo physical examinations, and blood samples are drawn to measure viral load. [AS PER AMENDMENT 4/27/00: Patients in Arms A1 and A2 may continue to receive medication for an additional 24 weeks. While on the treatment extension, patients must continue their current schedule for study drug administration and completion of study visits. Patients in Arms A1 and A2 who have reached Week 44 participate in an enteric-coated ddI pharmacokinetic study as part of this 24-week extension. Patients who were enrolled in Arms A1 or A2 and who were taken off study after reaching Week 48 may be re-entered onto the study at Week 52 regardless of the number of weeks they have been off study.]

• Study Type: Interventional
• Enrollment: 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00956
    • Ramon Ruiz Arnau Univ Hosp / Pediatrics
  • San Juan, Puerto Rico, 009367344
    • San Juan City Hosp
  • San Juan, Puerto Rico, 009365067
    • Univ of Puerto Rico / Univ Children's Hosp AIDS
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Univ of Alabama at Birmingham - Pediatric
    • Mobile, Alabama, United States, 36604
      • Univ of South Alabama
  • California
    • Long Beach, California, United States, 90801
      • Long Beach Memorial (Pediatric)
    • Los Angeles, California, United States, 90033
      • Los Angeles County - USC Med Ctr
    • Los Angeles, California, United States, 905022004
      • Harbor - UCLA Med Ctr / UCLA School of Medicine
    • Oakland, California, United States, 946091809
      • Children's Hosp of Oakland
    • San Francisco, California, United States, 941430105
      • UCSF / Moffitt Hosp - Pediatric
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard Univ Hosp
  • Florida
    • Fort Lauderdale, Florida, United States, 33311
      • North Broward Hosp District
    • Gainesville, Florida, United States, 32610
      • Univ of Florida Gainesville
    • Miami, Florida, United States, 33161
      • Univ of Miami (Pediatric)
  • Georgia
    • Atlanta, Georgia, United States, 30306
      • Emory Univ Hosp / Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
    • Chicago, Illinois, United States, 606143394
      • Chicago Children's Memorial Hosp
    • Chicago, Illinois, United States, 606371470
      • Univ of Chicago Children's Hosp
  • Louisiana
    • New Orleans, Louisiana, United States, 701122699
      • Tulane Univ / Charity Hosp of New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Earl K Long Early Intervention Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ of Maryland at Baltimore / Univ Med Ctr
    • Baltimore, Maryland, United States, 212874933
      • Johns Hopkins Hosp - Pediatric
  • Massachusetts
    • Boston, Massachusetts, United States, 021155724
      • Children's Hosp of Boston
    • Springfield, Massachusetts, United States, 01199
      • Baystate Med Ctr of Springfield
    • Worcester, Massachusetts, United States, 016550001
      • Univ of Massachusetts Med School
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hosp of Michigan
  • New Jersey
    • Newark, New Jersey, United States, 071032714
      • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
    • Newark, New Jersey, United States, 07103
      • Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
  • New York
    • Bronx, New York, United States, 10461
      • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
    • Bronx, New York, United States, 10457
      • Bronx Lebanon Hosp Ctr
    • Great Neck, New York, United States, 11021
      • North Shore Univ Hosp
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hosp
    • New York, New York, United States, 10016
      • Bellevue Hosp / New York Univ Med Ctr
    • New York, New York, United States, 10029
      • Metropolitan Hosp Ctr
    • New York, New York, United States, 10032
      • Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10032
      • Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10037
      • Harlem Hosp Ctr
    • Stony Brook, New York, United States, 117948111
      • State Univ of New York at Stony Brook
    • Syracuse, New York, United States, 13210
      • SUNY Health Sciences Ctr at Syracuse / Pediatrics
  • North Carolina
    • Durham, North Carolina, United States, 277103499
      • Duke Univ Med Ctr
  • South Carolina
    • Charleston, South Carolina, United States, 294253312
      • Med Univ of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 381052794
      • Saint Jude Children's Research Hosp of Memphis
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Med Ctr of Dallas
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hosp of the King's Daughters
    • Richmond, Virginia, United States, 23219
      • Med College of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients may be eligible for this study if they:

• Are between 4 months and 21 years of age (consent of parent or guardian required if under 18).
• Are HIV-positive.
• Have a viral level of at least 4,000 copies/ml.
• Have a CD4 cell count of at least 750 (under 12 months of age), at least 500 (1 to 5 years of age), or at least 200 (6 years of age or older) cells/mm3 within the past 4 months or a CD4 percent of 15 percent or higher within the past 4 months.
• Have received the same continuous antiretroviral therapy for the past 16 weeks.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have an active opportunistic and/or serious bacterial infection.
• Have been diagnosed with a malignancy.
• Have received prior treatment with certain antiretroviral medications.
• Are pregnant or breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• 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: Andrew Wiznia

Publications and helpful links

General Publications

• King JR, Nachman S, Yogev R, Hodge J, Aldrovandi G, Hughes MD, Chen J, Wiznia A, Damle B, Acosta EP. Efficacy, tolerability and pharmacokinetics of two nelfinavir-based regimens in human immunodeficiency virus-infected children and adolescents: pediatric AIDS clinical trials group protocol 403. Pediatr Infect Dis J. 2005 Oct;24(10):880-5. doi: 10.1097/01.inf.0000180508.21918.8a.

Study record dates

Study Major Dates

• Study Completion (Actual): June 1, 2001

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Anti-HIV Agents; HIV Protease Inhibitors
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Nevirapine; Ritonavir; Stavudine; Didanosine; Nelfinavir
• Other Study ID Numbers: ACTG 403; 11358 (Registry Identifier: DAIDS ES); P1001S (substudy); P1004S (substudy); PACTG 403