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

NCT ID: NCT00000872

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2005-01-31

Brief Summary

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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.

Detailed Description

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

Conditions

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HIV Infections

Keywords

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Abacavir sulfate

Intervention Type DRUG

Nelfinavir mesylate

Intervention Type DRUG

Nevirapine

Intervention Type DRUG

Lamivudine

Intervention Type DRUG

Stavudine

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

15 Days

Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katherine Luzuriaga

Role: STUDY_CHAIR

Locations

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Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy

Gainesville, Florida, United States

Site Status

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, United States

Site Status

Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases

Baltimore, Maryland, United States

Site Status

BMC, Div. of Ped Infectious Diseases

Boston, Massachusetts, United States

Site Status

Baystate Health, Baystate Med. Ctr.

Springfield, Massachusetts, United States

Site Status

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States

Site Status

Univ. of Mississippi Med. Ctr Children's Hosp.

Detroit, Michigan, United States

Site Status

Nyu Ny Nichd Crs

New York, New York, United States

Site Status

The Children's Hosp. of Philadelphia IMPAACT CRS

Philadelphia, Pennsylvania, United States

Site Status

Texas Children's Hosp. CRS

Houston, Texas, United States

Site Status

Children's Hosp. of the King's Daughters, Infectious Disease

Norfolk, Virginia, United States

Site Status

Countries

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Puerto Rico United States

References

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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)

Reference Type BACKGROUND

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)

Reference Type BACKGROUND

Luzuriaga K, Wu H, McManus M, Britto P, Borkowsky W, Burchett S, Smith B, Mofenson L, Sullivan JL. Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants. J Virol. 1999 Jan;73(1):362-7. doi: 10.1128/JVI.73.1.362-367.1999.

Reference Type BACKGROUND
PMID: 9847340 (View on PubMed)

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)

Reference Type BACKGROUND

Capparelli EV, Sullivan JL, Mofenson L, Smith E, Graham B, Britto P, Becker MI, Holland D, Connor JD, Luzuriaga K; Pediatric ACTG 356 Investigators. Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants. Pediatr Infect Dis J. 2001 Aug;20(8):746-51. doi: 10.1097/00006454-200108000-00006.

Reference Type BACKGROUND
PMID: 11734735 (View on PubMed)

Luzuriaga K, McManus M, Mofenson L, Britto P, Graham B, Sullivan JL; PACTG 356 Investigators. A trial of three antiretroviral regimens in HIV-1-infected children. N Engl J Med. 2004 Jun 10;350(24):2471-80. doi: 10.1056/NEJMoa032706.

Reference Type BACKGROUND
PMID: 15190139 (View on PubMed)

McManus M, Henderson J, Gautam A, Brody R, Weiss ER, Persaud D, Mick E, Luzuriaga K; PACTG 356 Investigators. Quantitative Human Immunodeficiency Virus (HIV)-1 Antibodies Correlate With Plasma HIV-1 RNA and Cell-associated DNA Levels in Children on Antiretroviral Therapy. Clin Infect Dis. 2019 May 2;68(10):1725-1732. doi: 10.1093/cid/ciy753.

Reference Type DERIVED
PMID: 30668843 (View on PubMed)

Other Identifiers

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10605

Identifier Type: REGISTRY

Identifier Source: secondary_id

PACTG 356

Identifier Type: -

Identifier Source: secondary_id

ACTG 356

Identifier Type: -

Identifier Source: org_study_id