Treatment With Combinations of Several Antiviral Drugs in Infants and Young Children With HIV Infection

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000872
First received: November 2, 1999
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

This trial tests the safety and effectiveness of the early use of combinations of anti-HIV drugs in HIV-infected infants and young children in an effort to block virus growth and preserve normal immune functions.

Various anti-HIV drug combinations need to be tested in order to find the best way to treat infants and children who have been infected with HIV during birth.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate
Drug: Nelfinavir mesylate
Drug: Nevirapine
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Early Intensive Antiretroviral Combination Therapy in HIV-1 Infected Infants and Children

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Antiretroviral activity of ZDV/3TC/NVP [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Durability of viral suppression [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Immune competence and HIV-1 specific immune respones with prolonged viral suppression beyond 104 weeks [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Antiretroviral activity of ZDV/3TC/NVP/1592U89 regimen [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Antiretroviral activity of d4T/3TC/NVP/NFV regimen [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Tolerance and pharmacokinetic profile of NFV [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Completion Date: January 2005
Detailed Description:

This study examines the antiretroviral activity of ZDV/3TC/NVP in vertically-infected infants and children aged 15 days up to 2 years, and ZDV/3TC/NVP/ABC in vertically-infected infants and children aged 30 days up to 2 years. This study will assess HIV-1 and CD4/CD8 T-cell kinetics, activation, and maturation. It will also test the concept that early (younger than 3 months of age) use of potent, combination antiretroviral therapy will allow the long-term control of viral replication with preservation of normal immune function. [AS PER AMENDMENT 3/11/98: This study will also examine the antiretroviral activity of ZDV/3TC/NVP/NFV in vertically infected infants and children.]

This is a 2-part Phase I/II, open-label trial in HIV-infected infants. Part A assesses the triple combination of ZDV, 3TC, and NVP. Four to eight patients are enrolled in each age cohort (Cohort 1: at least 15 days, no more than 3 months; Cohort 2: over 3 months, no more than 2 years). Part B assesses the quadruple combination of ZDV, 3TC, NVP, and ABC. Eight patients are enrolled in each age cohort (Cohort 3: at least 30 days, no more than 3 months; Cohort 4: over 3 months, no more than 2 years). [AS PER AMENDMENT 3/11/98: This study is now a 3-part Phase I/II trial. Parts A and B are as above. Part C will assess the quadruple regimen of d4T, 3TC, NVP and NFV. Up to 8 patients will be enrolled in each age cohort (Cohort 5: at least 15 days, no more than 3 months; Cohort 6: over 3 months, no more than 2 years). If 3 of 4 patients in either cohort of Part B do not achieve plasma RNA less than 1,000 copies/ml after 16 weeks of quadruple therapy, enrollment of patients to that cohort will stop and enrollment of 8 patients to the corresponding cohort in Part C will begin. For Part C, patients whose RNA level is no more than 1,000 copies/ml at Week 16 will remain on assigned treatment until Week 104. If at any time between Weeks 16 and 104 a patient's RNA level increases to greater than 1,000 copies/ml, plasma RNA will be repeated within 1 week. If both RNA levels are greater than 1,000 copies/ml, the patient will discontinue study treatment and be followed every 12 weeks for 1 year.] [AS PER AMENDMENT 4/14/99: The study has been extended for an additional 96 weeks for children with continued suppression of viral replication (RNA less than 400 copies/ml) at Week 104. If at any time between Week 12 or 16 and Week 200 a patient's RNA level increases to greater than 1,000 copies/ml, plasma RNA will be repeated within 1 week. If both RNA levels are above 1,000 copies/ml, the patient will discontinue treatment for best available therapy and be followed every 12 weeks for 1 year following the discontinuation of study treatment.] [AS PER AMENDMENT 9/16/99: An additional cohort (Cohort 7) of 5 to 10 patients has been added. Cohort 7 includes patients between 15 days and 3 months of age. Cohort 7 patients who experience suppression of viral replication at Week 104 are followed through Week 200.]

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Children may be eligible for this study if they:

  • Are 15 days to 2 years old.
  • Have consent of parent or legal guardian.
  • Are HIV-positive.

Exclusion Criteria

Children will not be eligible for this study if they:

  • Have certain infections which require treatment during the study.
  • Have received certain medications.
  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: NCT00000872

Locations
United States, Florida
Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy
Gainesville, Florida, United States, 32209
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
Baltimore, Maryland, United States, 21201
Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
Baltimore, Maryland, United States, 212874933
United States, Massachusetts
BMC, Div. of Ped Infectious Diseases
Boston, Massachusetts, United States, 02118
Baystate Health, Baystate Med. Ctr.
Springfield, Massachusetts, United States, 01199
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States, 016550001
United States, Michigan
Univ. of Mississippi Med. Ctr Children's Hosp.
Detroit, Michigan, United States
United States, New York
Nyu Ny Nichd Crs
New York, New York, United States
United States, Pennsylvania
The Children's Hosp. of Philadelphia IMPAACT CRS
Philadelphia, Pennsylvania, United States, 191044318
United States, Texas
Texas Children's Hosp. CRS
Houston, Texas, United States, 77030
United States, Virginia
Children's Hosp. of the King's Daughters, Infectious Disease
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
Investigators
Study Chair: Katherine Luzuriaga
  More Information

Additional Information:
Publications:
Luzuriaga K, McManus M, Britto P, Wu HL, Lindsey J, Sullivan JL. Viral kinetics and control of replication following potent early combination antiretroviral therapy of vertical HIV-1 infection. HIV Pathog Treat Conf. 1998 Mar 13-19;52 (abstract no 2024)
Capparelli E, Sullivan J, Mofenson L, Smith B, Graham B, Britto P, Becker M, Luzuriaga K. Pharmacokinetics (PK) of nelfinavir and its metabolite (M8) in HIV-infected infants following BID or TID administration. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 729)
Luzuriaga K, Mcmanus M, Britto P, Wu H, Lindsey J, Smith B, Mofenson L, Sullivan JL. Early combination antiretroviral therapy of vertical HIV-1 infection: viral kinetics and control of viral replication. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:225 (abstract no LB12)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000872     History of Changes
Other Study ID Numbers: ACTG 356, 10605, PACTG 356
Study First Received: November 2, 1999
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Virus Replication
HIV-1
Drug Therapy, Combination
Zidovudine
Nevirapine
Stavudine
HIV Protease Inhibitors
CD4 Lymphocyte Count
Lamivudine
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Nelfinavir

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
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
Lamivudine
Nelfinavir
Nevirapine
Reverse Transcriptase Inhibitors
Stavudine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 29, 2014