Comparison of New Anti-HIV Drug Combinations in HIV-Infected Children Who Have Taken Anti-HIV Drugs

NCT00001083 | Completed Phase 2

• 2 other identifiers: ACTG 33811309
• Study Type: interventional
• Target: 240
• Locations: 2 countries
• Sites: 61

Brief Summary

For PRAM-1: To evaluate zidovudine (ZDV) + lamivudine (3TC) vs. stavudine (d4T) + ritonavir vs. ZDV + 3TC + ritonavir with respect to the change in plasma HIV-1 RNA copy number from baseline to 48 weeks \[AS PER AMENDMENT 1/5/98: 72 weeks; AS PER AMENDMENT 7/17/98: 48 weeks\] in stable HIV-infected children with \>= 16 weeks of prior continuous antiretroviral therapy. To evaluate the safety and tolerance of ZDV + 3TC vs. d4T + ritonavir vs. ZDV + 3TC + ritonavir based upon laboratory and clinical toxicities. AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: To evaluate d4T + nevirapine + ritonavir with respect to change in plasma HIV-1 RNA copy number from baseline to 48 weeks in children who have received at least 12 weeks of therapy on the PRAM-1 ZDV/3TC arm and have over 10,000 viral copies at weeks 12, 24, or 36. To evaluate the safety and tolerance of d4T + nevirapine + ritonavir based upon laboratory and clinical toxicities. \[AS PER AMENDMENT 10/23/98: To evaluate safety and tolerance of a switch from d4T + ritonavir vs. ZDV + 3TC + ritonavir to d4T + indinavir vs. ZDV + 3TC + indinavir in stable, HIV-infected children with RNA values \<= 10,000 copies/ml.\] For PRAM-1: Evidence supports combination therapy with 2 or more antiviral agents as beneficial in the long-term management of HIV. The possibility exists that combination therapy may result in a synergistic or additive activity over a prolonged period of time. Also hypothesized is that the development of resistance to individual agents will be developed if viral replication is significantly decreased. AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: Interim analysis at 12 weeks on PRAM-1 indicates that the proportion of children reaching undetectable RNA levels on the ZDV + 3TC arm is significantly less than the other two arms. The protocol, therefore, has been modified (Step 2) to permit children in the ZDV + 3TC arm with RNA copy number \>= 10,000 the opportunity to change to a novel therapeutic regimen (d4T + nevirapine + ritonavir).

Conditions

HIV Infections

Keywords

HIV-1; Drug Therapy, Combination; Zidovudine; Nevirapine; Stavudine; HIV Protease Inhibitors; Ritonavir; Lamivudine; Indinavir; RNA, Viral; Reverse Transcriptase Inhibitors; Anti-HIV Agents

Interventions

Indinavir sulfate DRUG

Ritonavir DRUG

Nevirapine DRUG

Lamivudine DRUG

Stavudine DRUG

Zidovudine DRUG

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Concurrent Medication:
• Allowed:
• IVIG and opportunistic infection prophylaxis will be allowed.
• Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony- stimulating factor (GM-CSF) will be allowed for the management of hematologic toxicity.
• Treatment with trimethoprim is allowed at the discretion of the principal investigator.
• Patients must have:
• Laboratory evidence (at least 2 viral tests) of HIV-1 infection.
• Clinical and immunological stability \[maintained CDC category 1 or 2 immunologic status for past 4 months and no new CDC category (diagnosis within the past year)\].
• Patients must have received continuous antiretroviral therapy for the past 16 weeks (missing no more than 6 weeks of therapy during the previous 16 weeks).
• AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2:
• Viral load \>= 10,000 and \< 100,000 copies/ml at week 12, 24, or 36 in children initially assigned to Arm I (ZDV + 3TC) of PRAM-1 and currently on study.
• Prior Medication:
• Required:
• Patients must have received continuous antiretroviral therapy for the past 16 weeks.
• Allowed:

You may not qualify if:

• Co-existing Condition:
• Patients with the following symptoms or conditions are excluded:
• Current grade 3/4 clinical or laboratory toxicity and/or current grade 2 or higher amylase/lipase toxicity.
• Active opportunistic infection and/or serious bacterial infection.
• Current diagnosis of malignancy.
• Concurrent Medication:
• Excluded:
• Current antiretroviral therapy identical to any of the following regimens:
• ZDV + 3TC, d4T + ritonavir and ZDV + 3TC + ritonavir.
• Concurrent therapy with any other anti-HIV-1 therapy, biologic response modifiers (EPO, G-CSF and GM-CSF allowed), human growth hormone and megestrol acetate.
• Use of continuous systemic corticosteroids (\>= 14 days duration) is not allowed.
• Medications that are incompatible with ritonavir.
• Probenecid and daily intravenous pentamidine.
• \[AS PER AMENDMENT 10/23/98: The following are excluded in patients receiving indinavir:
• terfenadine, astemizole, cisapride, rifampin, rifabutin, triazolam, ketoconazole, clarithromycin, carbamazepine, phenobarbital, phenytoin, calcium channel blockers, midazolam, and ergot derivatives.\]

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (61)

Univ of Alabama at Birmingham - Pediatric

Birmingham, Alabama, 35233, United States

Location

UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, 920930672, United States

Location

Long Beach Memorial (Pediatric)

Long Beach, California, 90801, United States

Location

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, 900276016, United States

Location

Los Angeles County - USC Med Ctr

Los Angeles, California, 90033, United States

Location

UCLA Med Ctr / Pediatric

Los Angeles, California, 900951752, United States

Location

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, 905022004, United States

Location

Children's Hosp of Oakland

Oakland, California, 946091809, United States

Location

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, 941430105, United States

Location

Univ of Connecticut / Farmington

Farmington, Connecticut, 06032, United States

Location

Yale Univ Med School

New Haven, Connecticut, 06504, United States

Location

Children's Hosp of Washington DC

Washington D.C., District of Columbia, 200102916, United States

Location

Howard Univ Hosp

Washington D.C., District of Columbia, 20060, United States

Location

North Broward Hosp District

Fort Lauderdale, Florida, 33311, United States

Location

Univ of Florida Gainesville

Gainesville, Florida, 32610, United States

Location

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, 32209, United States

Location

Univ of Miami (Pediatric)

Miami, Florida, 33161, United States

Location

Palm Beach County Health Dept

Riviera Beach, Florida, 33404, United States

Location

Emory Univ Hosp / Pediatrics

Atlanta, Georgia, 30306, United States

Location

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, 60612, United States

Location

Chicago Children's Memorial Hosp

Chicago, Illinois, 606143394, United States

Location

Univ of Chicago Children's Hosp

Chicago, Illinois, 606371470, United States

Location

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, 701122699, United States

Location

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, 21201, United States

Location

Children's Hosp of Boston

Boston, Massachusetts, 021155724, United States

Location

Boston City Hosp / Pediatrics

Boston, Massachusetts, 02118, United States

Location

Baystate Med Ctr of Springfield

Springfield, Massachusetts, 01199, United States

Location

Univ of Massachusetts Med School

Worcester, Massachusetts, 016550001, United States

Location

Univ of Mississippi Med Ctr

Jackson, Mississippi, 39213, United States

Location

UMDNJ - Robert Wood Johnson Med School / Pediatrics

New Brunswick, New Jersey, 089030019, United States

Location

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, 071032714, United States

Location

Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl

Newark, New Jersey, 07103, United States

Location

Children's Hosp at Albany Med Ctr

Albany, New York, 12208, United States

Location

King's County Hosp Ctr / Pediatrics

Brooklyn, New York, 11203, United States

Location

SUNY - Brooklyn

Brooklyn, New York, 11203, United States

Location

North Shore Univ Hosp

Great Neck, New York, 11021, United States

Location

Schneider Children's Hosp

New Hyde Park, New York, 11040, United States

Location

Bellevue Hosp / New York Univ Med Ctr

New York, New York, 10016, United States

Location

Cornell Univ Med College

New York, New York, 10021, United States

Location

Metropolitan Hosp Ctr

New York, New York, 10029, United States

Location

Mount Sinai Med Ctr / Pediatrics

New York, New York, 10029, United States

Location

Columbia Presbyterian Med Ctr

New York, New York, 10032, United States

Location

Incarnation Children's Ctr / Columbia Presbyterian Med Ctr

New York, New York, 10032, United States

Location

Harlem Hosp Ctr

New York, New York, 10037, United States

Location

Univ of Rochester Med Ctr

Rochester, New York, 146420001, United States

Location

State Univ of New York at Stony Brook

Stony Brook, New York, 117948111, United States

Location

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, 13210, United States

Location

Bronx Lebanon Hosp Ctr

The Bronx, New York, 10457, United States

Location

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, 10461, United States

Location

Westchester Hosp

Valhalla, New York, 10595, United States

Location

Duke Univ Med Ctr

Durham, North Carolina, 277103499, United States

Location

Columbus Children's Hosp

Columbus, Ohio, 432052696, United States

Location

Saint Christopher's Hosp for Children

Philadelphia, Pennsylvania, 191341095, United States

Location

Med Univ of South Carolina

Charleston, South Carolina, 294253312, United States

Location

Children's Med Ctr of Dallas

Dallas, Texas, 75235, United States

Location

Texas Children's Hosp / Baylor Univ

Houston, Texas, 77030, United States

Location

Med College of Virginia

Richmond, Virginia, 23219, United States

Location

Children's Hospital & Medical Center / Seattle ACTU

Seattle, Washington, 981050371, United States

Location

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, 00956, Puerto Rico

Location

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, 009365067, Puerto Rico

Location

San Juan City Hosp

San Juan, 009367344, Puerto Rico

Location

Related Publications (6)

• Nachman S. Lack of improvement in growth in HIV-infected children on HAART 39th Intersci Conf Antimicrob Agents Chemother. 1999 Sept 26-29 (abstract no 120)

  RESULT

• Yogev R, Lee S, Wiznia A, Nachman S, Stanley K, Pelton S, Mofenson L, Fiscus S, Jimenez E, Rathore MH, Smith ME, Song LY, McIntosh K; Pediatrics AIDS Clinical Trials Group 338 Study Team. Stavudine, nevirapine and ritonavir in stable antiretroviral therapy-experienced children with human immunodeficiency virus infection. Pediatr Infect Dis J. 2002 Feb;21(2):119-25. doi: 10.1097/00006454-200202000-00007.

  PMID: 11840078 RESULT

• Nachman SA, Stanley K, Yogev R, Pelton S, Wiznia A, Lee S, Mofenson L, Fiscus S, Rathore M, Jimenez E, Borkowsky W, Pitt J, Smith ME, Wells B, McIntosh K. Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team. JAMA. 2000 Jan 26;283(4):492-8. doi: 10.1001/jama.283.4.492.

  PMID: 10659875 RESULT

• Nachman SA, Lindsey JC, Pelton S, Mofenson L, McIntosh K, Wiznia A, Stanley K, Yogev R. Growth in human immunodeficiency virus-infected children receiving ritonavir-containing antiretroviral therapy. Arch Pediatr Adolesc Med. 2002 May;156(5):497-503. doi: 10.1001/archpedi.156.5.497.

  PMID: 11980557 RESULT

• Jeremy RJ, Kim S, Nozyce M, Nachman S, McIntosh K, Pelton SI, Yogev R, Wiznia A, Johnson GM, Krogstad P, Stanley K; Pediatric AIDS Clinical Trials Group (PACTG) 338 & 377 Study Teams. Neuropsychological functioning and viral load in stable antiretroviral therapy-experienced HIV-infected children. Pediatrics. 2005 Feb;115(2):380-7. doi: 10.1542/peds.2004-1108.

  PMID: 15687448 RESULT

• Fiscus SA, Kovacs A, Petch LA, Hu C, Wiznia AA, Mofenson LM, Yogev R, McIntosh K, Pelton SI, Napravnik S, Stanley K, Nachman SA. Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338). AIDS Res Ther. 2007 Feb 6;4:2. doi: 10.1186/1742-6405-4-2.

  PMID: 17280617 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Indinavir; Ritonavir; Nevirapine; Lamivudine; Stavudine; Zidovudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Thymidine

Study Officials

• Nachman S

  STUDY CHAIR

• Wiznia A

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: June 1, 2001
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

PR (3); US (58)