Anti-HIV Drug Regimens and Treatment-Switching Guidelines in HIV Infected Children

NCT00039741 | Completed Phase 2 Results

• 4 other identifiers: P390PENPACT-1B10106PENTA 9/PACTG 390
• Study Type: interventional
• Target: 266
• Locations: 2 countries
• Sites: 31

Brief Summary

Little is known about what treatment combinations are best for HIV infected children. This study examined the long-term effectiveness of different anti-HIV drug combinations in children and strategies for switching treatment if the first treatment does not work. The study enrolled children who had not previously taken anti-HIV medication. Participants in this study were recruited in the United States, South America and Europe. Some European children may also enroll in a substudy that will observe changes in body fat in children taking anti-HIV medications.

Conditions

HIV Infections

Keywords

Drug Therapy, Combination; HIV Protease Inhibitors; Reverse Transcriptase Inhibitors; Viral Load; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• Change in Viral Load Measured in log10 HIV-1 RNA Copies/ml

  Baseline visit and 4 years after Study Entry

Secondary Outcomes (8)

• Rate of Grade 3 or Higher Signs, Symptoms, or Laboratory Abnormalities Experienced

  Up to 6 yrs. (average 4.85 yrs.)

• Participants With Significant HIV-related Clinical Events, Defined as CDC Category C (AIDS Defining) Diagnoses (Except for Recurrent Bacterial Infections)or Death

  Up to 6 yrs. (average 4.85 yrs.)

• Time to Switching to an Alternative Class ART Regimen (Based on Initial Randomized Regimen)

  Up to 6 yrs. (average 4.85 yrs.)

• Time to HIV-1 RNA of 400 Copies/ml or Greater During First-line Therapy or Permanent Discontinuation of First-line Therapy

  Up to 6 yrs. (average 4.85 yrs.)

• Time to HIV-1 RNA of 30,000 Copies/ml or Greater During Second-line Therapy or Permanent Discontinuation of Second-line Therapy

  Up to 6 yrs. (average 4.85 yrs.)

Study Arms (4)

PI/1K

EXPERIMENTAL

Two NRTIs plus a PI with a regimen change recommended at when viral load reaches 1000 copies/ml or higher

Drug: NRTIs (ABC, FTC, FTC/TDF, 3TC, 3TC/AZT, d4T, TDF, ddC, AZT); Drug: PIs (AMP, IDV, LPV/r, NFV, SQV, RTV)

NNRTI/1K

EXPERIMENTAL

2 NRTIs plus an NNRTI with a regimen change recommended when viral load reaches 1,000 copies/ml or higher

Drug: NRTIs (ABC, FTC, FTC/TDF, 3TC, 3TC/AZT, d4T, TDF, ddC, AZT); Drug: NNRTIs (EFV, NVP)

PI/30K

EXPERIMENTAL

2 NRTIs plus 1 PI with a regimen change recommended when viral load reaches 30,000 copies/ml or higher

Drug: NRTIs (ABC, FTC, FTC/TDF, 3TC, 3TC/AZT, d4T, TDF, ddC, AZT); Drug: PIs (AMP, IDV, LPV/r, NFV, SQV, RTV)

NNRTI/30K

EXPERIMENTAL

2 NRTIs plus an NNRTI with a regimen change recommended when viral load reaches 30,000 copies/ml or higher

Drug: NRTIs (ABC, FTC, FTC/TDF, 3TC, 3TC/AZT, d4T, TDF, ddC, AZT); Drug: NNRTIs (EFV, NVP)

Interventions

NRTIs (ABC, FTC, FTC/TDF, 3TC, 3TC/AZT, d4T, TDF, ddC, AZT) DRUG

Accepted NRTIs: abacavir sulfate (ABC), emtricitabine (FTC), emtricitabine/Tenofovir disoproxil fumarate (FTC/TDF), lamivudine (3TC), lamivudine/zidovudine (3TC/AZT), stavudine (d4T), tenofovir disoproxil fumarate (TDF), zalcitabine (ddC), zidovudine (AZT) Prescribed per participant's doctor

Also known as: 2 NRTIs/PI, change@viral load 1000 copies/ml or higher, 2 NRTIs/PI, change@viral load 30,000 copies/ml or higher, 2 NRTIs/NNRTI, change@viral load 1000 copies/ml or higher, 2 NRTIs/NNRTI, change@viral load 30,000 copies/ml or higher

NNRTI/1K; NNRTI/30K; PI/1K; PI/30K

NNRTIs (EFV, NVP) DRUG

Accepted NNRTIs: efavirenz (EFV), nevirapine (NVP) Prescribed per participant's doctor

Also known as: 2 NRTIs/NNRTI, change@viral load 1000 copies/ml or higher, 2 NRTIs/NNRTI, change@viral load 30,000 copies/ml or higher

NNRTI/1K; NNRTI/30K

PIs (AMP, IDV, LPV/r, NFV, SQV, RTV) DRUG

Accepted PIs: amprenavir (APV). indinavir sulfate (IDV), lopinavir/ritonavir (LPV/r), nelfinavir mesylate (NFV), saquinavir (SQV), ritonavir (RTV) Prescribed per participant's doctor

Also known as: 2 NRTIs/PI, change@viral load 1000 copies/ml or higher, 2 NRTIs/PI, change@viral load 30,000 copies/ml or higher

PI/1K; PI/30K

Eligibility Criteria

• Age: 30 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Older than 30 days and younger than 18 years of age (may enroll up to the day before their 18th birthday)
• HIV infected
• Not previously on HAART or received anti-HIV drugs for less than 56 consecutive days after birth to prevent mother-to-infant HIV transmission. Participants who have previously received nevirapine for the prevention of mother-to-infant HIV transmission are not eligible for this study.
• Willing to use acceptable methods of contraception

You may not qualify if:

• Grade 3 or 4 clinical or laboratory toxicity. More information on this criterion can be found in the protocol.
• Active opportunistic infection or a serious bacterial infection at the time of study entry
• Pancreas, nervous system, blood, liver, or kidney problems that make it impossible to take study medications
• Taking any medication that cannot be combined with the study medications in first-line therapy
• Received therapy for cancer
• Pregnant or breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• PENTA Foundation: collaborator

Study Sites (31)

Usc La Nichd Crs

Alhambra, California, 91803, United States

Location

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, 90806, United States

Location

Children's Hospital of Los Angeles NICHD CRS

Los Angeles, California, 90027-6062, United States

Location

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

Los Angeles, California, 90095-1752, United States

Location

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.

Oakland, California, 94609, United States

Location

Connecticut Children's Med. Ctr.

Hartford, Connecticut, 06106, United States

Location

Howard Univ. Washington DC NICHD CRS

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

Location

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, 33316, United States

Location

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

Gainesville, Florida, 32610-0296, United States

Location

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, 33136, United States

Location

USF - Tampa NICHD CRS

Tampa, Florida, 33606, United States

Location

Chicago Children's CRS

Chicago, Illinois, 60614, United States

Location

Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease

Chicago, Illinois, 60637, United States

Location

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, 70112, United States

Location

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, 01605, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

UMDNJ - Robert Wood Johnson Med. School, Div. of Allergy, Immunology & Infectious Diseases

New Brunswick, New Jersey, 08901-1969, United States

Location

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, 07103, United States

Location

Nyu Ny Nichd Crs

New York, New York, 10016, United States

Location

Columbia IMPAACT CRS

New York, New York, 10032, United States

Location

Harlem Hosp. Ctr. NY NICHD CRS

New York, New York, 10037, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794-8111, United States

Location

SUNY Upstate Med. Univ., Dept. of Peds.

Syracuse, New York, 13210, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases

Chapel Hill, North Carolina, 27599-7220, United States

Location

Oregon Health & Science Univ. - Dept. of Peds., Div. of Infectious Disease

Portland, Oregon, 97239, United States

Location

St. Jude/UTHSC CRS

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hospital CRS

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital CRS

Seattle, Washington, 98105, United States

Location

Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS

San Juan, 00935, Puerto Rico

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Related Publications (5)

• Brogly S, Williams P, Seage GR 3rd, Oleske JM, Van Dyke R, McIntosh K; PACTG 219C Team. Antiretroviral treatment in pediatric HIV infection in the United States: from clinical trials to clinical practice. JAMA. 2005 May 11;293(18):2213-20. doi: 10.1001/jama.293.18.2213.

  PMID: 15886376 BACKGROUND

• Havens PL. Principles of antiretroviral treatment of children and adolescents with human immunodeficiency virus infection. Semin Pediatr Infect Dis. 2003 Oct;14(4):269-85. doi: 10.1053/j.spid.2003.09.005.

  PMID: 14724792 BACKGROUND

• Hoody DW, Fletcher CV. Pharmacology considerations for antiretroviral therapy in human immunodeficiency virus (HIV)-infected children. Semin Pediatr Infect Dis. 2003 Oct;14(4):286-94. doi: 10.1053/j.spid.2003.09.004.

  PMID: 14724793 BACKGROUND

• McKinney RE Jr, Cunningham CK. Newer treatments for HIV in children. Curr Opin Pediatr. 2004 Feb;16(1):76-9. doi: 10.1097/00008480-200402000-00014.

  PMID: 14758118 BACKGROUND

• PENPACT-1 (PENTA 9/PACTG 390) Study Team; Babiker A, Castro nee Green H, Compagnucci A, Fiscus S, Giaquinto C, Gibb DM, Harper L, Harrison L, Hughes M, McKinney R, Melvin A, Mofenson L, Saidi Y, Smith ME, Tudor-Williams G, Walker AS. First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial. Lancet Infect Dis. 2011 Apr;11(4):273-83. doi: 10.1016/S1473-3099(10)70313-3. Epub 2011 Jan 31.

  PMID: 21288774 RESULT

Related Links

• Click here for more information about ACTG 219C (NCT00006304)

MeSH Terms

Conditions

HIV Infections

Interventions

abacavir; Racivir; Stavudine; efavirenz; Nevirapine; CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; Adenosine Monophosphate; Indinavir; Nelfinavir; Saquinavir; Ritonavir

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)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pyridines; Transferases (Other Substituted Phosphate Groups); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleotides; Ribonucleotides; Isoquinolines; Quinolines; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• Ross E. McKinney, Jr., MD

  Duke University

  STUDY CHAIR

• Ann J. Melvin, MD

  Division of Infectious Diseases, Children's Hospital and Medical Center, Seattle, WA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2002
• First Posted: June 11, 2002
• Study Start: August 1, 2002
• Primary Completion: August 1, 2009
• Study Completion: March 1, 2010
• Last Updated: November 5, 2021
• Results First Posted: April 24, 2012

Record last verified: 2019-01

Locations

PR (2); US (29)