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

NCT ID: NCT00039741

Last Updated: 2021-11-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

266 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-08-31

Study Completion Date

2010-03-31

Brief Summary

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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.

Detailed Description

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Antiretroviral therapy in children aims to prolong clinical and immunologic health. Currently, there are no data defining a particular highly active antiretroviral therapy (HAART) strategy as the optimal first-line therapy for children. This study evaluated the long-term efficacy of two HAART regimens used as initial therapy: 1) two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI), and 2) two NRTIs plus a nonnucleoside reverse transcriptase inhibitor (NNRTI). It also evaluated different strategies for switching therapy when the initial regimen fails. The long-term nature of this study should clarify whether early switching of therapy improves immunologic and virologic outcomes, or results in a more rapid exhaustion of treatment options. The study was conducted in the United States and in Europe.

Participants in this study had a CD4 cell count and viral load test during a screening visit. Participants had an entry visit that included blood and urine tests. Participants were then randomly assigned to one of four groups: Groups PI/1K and PI/30K received two NRTIs plus a PI; Groups NNRTI/1K and NNRTI/30K received two NRTIs plus an NNRTI. The medications allowed in the study were: abacavir, didanosine, emtricitabine, emtricitabine/tenofovir disoproxil fumarate, lamivudine, lamivudine/zidovudine, stavudine, tenofovir disoproxil fumarate, zalcitabine, and zidovudine (NRTIs); efavirenz and nevirapine (NNRTIs); efavirenz/emtricitabine/tenofovir disoproxil fumurate (NNRTI/NRTI); and amprenavir,atazanavir, darunavir, fosamprenavir calcium, indinavir, lopinavir/ritonavir, nelfinavir, saquinavir, ritonavir, and tipranavir (PIs). Note: Per the 06/28/05 amendment of this trial, emtricitabine, emtricitabine/tenofovir disoproxil fumarate, and tenofovir dioproxil fumarate were added to the list of medications that could be included in a participant's treatment regimen.

For participants whose initial regimen failed, or who experienced clinical disease progression (indicated by the development of a new CDC Category C diagnosis) or other clinical disease progression at or after Week 24 of first-line therapy, second-line therapy was strongly encouraged. (However, if poor adherence was suspected as a possible reason for an increase in HIV viral load, the site and the clinician were to try to improve patient adherence and obtain additional confirmatory viral load values within a five-week time frame.) In second-line therapy, participants who initially took NRTIs with a PI switched to NRTIs and an NNRTI. Participants who initially took NRTIs and an NNRTI switched to NRTIs and a PI. The timing of the switch was based on the participant's group: Groups PI/1K and NNRTI/1K switched to second-line treatment when viral load was 1,000 copies/ml or greater; Groups PI/30K and NNRTI/30K switched to second-line treatment when viral load was 30,000 copies/ml or greater. Participants who failed second-line therapy discontinued study treatment and were offered the best available therapy at the discretion of the clinician.

Participants had study visits at Weeks 2, 4, 8, 12, 16, 24, and every 12 weeks thereafter until the drug regimen was switched to second-line treatment. Participants then had a re-entry visit and the schedule of visits restarted. Participants were in the study between 4 and 7 years, depending on when they enrolled. All study visits included medical history, a physical exam, and blood collection. Urine collection occurred at most visits. Participants were asked to complete adherence questionnaires and PACTG participants underwent neuropsychological assessments at selected visits.

All participants in this study were encouraged to coenroll in PACTG 219C, Long-Term Effects of HIV Exposure and Infection in Children. Participants in the European portion of the study may be asked to enroll in a substudy to observe the development and progression of lipodystrophy syndrome in children.

Conditions

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HIV Infections

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PI/1K

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

Group Type EXPERIMENTAL

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

Intervention Type 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

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

Intervention Type DRUG

Accepted PIs: amprenavir (APV). indinavir sulfate (IDV), lopinavir/ritonavir (LPV/r), nelfinavir mesylate (NFV), saquinavir (SQV), ritonavir (RTV)

Prescribed per participant's doctor

NNRTI/1K

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

Group Type EXPERIMENTAL

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

Intervention Type 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

NNRTIs (EFV, NVP)

Intervention Type DRUG

Accepted NNRTIs: efavirenz (EFV), nevirapine (NVP)

Prescribed per participant's doctor

PI/30K

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

Group Type EXPERIMENTAL

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

Intervention Type 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

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

Intervention Type DRUG

Accepted PIs: amprenavir (APV). indinavir sulfate (IDV), lopinavir/ritonavir (LPV/r), nelfinavir mesylate (NFV), saquinavir (SQV), ritonavir (RTV)

Prescribed per participant's doctor

NNRTI/30K

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

Group Type EXPERIMENTAL

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

Intervention Type 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

NNRTIs (EFV, NVP)

Intervention Type DRUG

Accepted NNRTIs: efavirenz (EFV), nevirapine (NVP)

Prescribed per participant's doctor

Interventions

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

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

Intervention Type DRUG

NNRTIs (EFV, NVP)

Accepted NNRTIs: efavirenz (EFV), nevirapine (NVP)

Prescribed per participant's doctor

Intervention Type DRUG

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

Accepted PIs: amprenavir (APV). indinavir sulfate (IDV), lopinavir/ritonavir (LPV/r), nelfinavir mesylate (NFV), saquinavir (SQV), ritonavir (RTV)

Prescribed per participant's doctor

Intervention Type DRUG

Other Intervention Names

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

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

30 Days

Maximum Eligible Age

18 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

PENTA Foundation

NETWORK

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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Ross E. McKinney, Jr., MD

Role: STUDY_CHAIR

Duke University

Ann J. Melvin, MD

Role: STUDY_CHAIR

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

Locations

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Usc La Nichd Crs

Alhambra, California, United States

Site Status

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, United States

Site Status

Children's Hospital of Los Angeles NICHD CRS

Los Angeles, California, United States

Site Status

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

Los Angeles, California, United States

Site Status

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

Oakland, California, United States

Site Status

Connecticut Children's Med. Ctr.

Hartford, Connecticut, United States

Site Status

Howard Univ. Washington DC NICHD CRS

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

Site Status

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, United States

Site Status

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

Gainesville, Florida, United States

Site Status

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, United States

Site Status

USF - Tampa NICHD CRS

Tampa, Florida, United States

Site Status

Chicago Children's CRS

Chicago, Illinois, United States

Site Status

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

Chicago, Illinois, United States

Site Status

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, United States

Site Status

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States

Site Status

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

Site Status

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

New Brunswick, New Jersey, United States

Site Status

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, United States

Site Status

Nyu Ny Nichd Crs

New York, New York, United States

Site Status

Columbia IMPAACT CRS

New York, New York, United States

Site Status

Harlem Hosp. Ctr. NY NICHD CRS

New York, New York, United States

Site Status

SUNY Stony Brook NICHD CRS

Stony Brook, New York, United States

Site Status

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

Syracuse, New York, United States

Site Status

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, United States

Site Status

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

Chapel Hill, North Carolina, United States

Site Status

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

Portland, Oregon, United States

Site Status

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Site Status

Texas Children's Hospital CRS

Houston, Texas, United States

Site Status

Seattle Children's Hospital CRS

Seattle, Washington, United States

Site Status

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

San Juan, , Puerto Rico

Site Status

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Site Status

Countries

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Brazil The Bahamas United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 15886376 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14724792 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14724793 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14758118 (View on PubMed)

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.

Reference Type RESULT
PMID: 21288774 (View on PubMed)

Related Links

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http://www.clinicaltrials.gov/ct/show/NCT00006304

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

Other Identifiers

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PENPACT-1B

Identifier Type: -

Identifier Source: secondary_id

10106

Identifier Type: REGISTRY

Identifier Source: secondary_id

PENTA 9/PACTG 390

Identifier Type: -

Identifier Source: secondary_id

P390

Identifier Type: -

Identifier Source: org_study_id