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

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

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

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Ross E. McKinney, Jr., MD, Study Chair, Affiliation: Duke University
Ann J. Melvin, MD, Study Chair, Affiliation: Division of Infectious Diseases, Children's Hospital and Medical Center, Seattle, WA

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.

Clinical Details

Official title: A Phase II/III Randomized, Open-Label Study of Combination Antiretroviral Regimens and Treatment-Switching Strategies in HIV-1-Infected Antiretroviral Naive Children Between 30 Days and 18 Years of Age

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in Viral Load Measured in log10 HIV-1 RNA Copies/ml

Secondary outcome:

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

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

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

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

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

Number of Children With an HIV-1 RNA Level Less Than 400 Copies/ml Regardless of Therapy at Week 204

Change in CD4% From Randomization to 4 Years

Number of Children With HIV-1 RNA Less Than 400 Copies/ml and on Original Randomized Therapy at 24 Weeks

Detailed description: 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.

Eligibility

Minimum age: N/A. Maximum age: 18 Years. Gender(s): Both.

Criteria:

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

Locations and Contacts

San Juan City Hosp. PR NICHD CRS, San Juan 00936, Puerto Rico

Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS, San Juan 00935, Puerto Rico

Usc La Nichd Crs, Alhambra, California 91803, United States

Miller Children's Hosp. Long Beach CA NICHD CRS, Long Beach, California 90806, United States

Children's Hospital of Los Angeles NICHD CRS, Los Angeles, California 90027-6062, United States

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS, Los Angeles, California 90095-1752, United States

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab., Oakland, California 94609, United States

Connecticut Children's Med. Ctr., Hartford, Connecticut 06106, United States

Howard Univ. Washington DC NICHD CRS, Washington, District of Columbia 20060, United States

South Florida CDTC Ft Lauderdale NICHD CRS, Fort Lauderdale, Florida 33316, United States

Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy, Gainesville, Florida 32610-0296, United States

Univ. of Miami Ped. Perinatal HIV/AIDS CRS, Miami, Florida 33136, United States

USF - Tampa NICHD CRS, Tampa, Florida 33606, United States

Chicago Children's CRS, Chicago, Illinois 60614, United States

Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease, Chicago, Illinois 60637, United States

Tulane Univ. New Orleans NICHD CRS, New Orleans, Louisiana 70112, United States

WNE Maternal Pediatric Adolescent AIDS CRS, Worcester, Massachusetts 01605, United States

Washington U CRS, St. Louis, Missouri 63110, United States

UMDNJ - Robert Wood Johnson Med. School, Div. of Allergy, Immunology & Infectious Diseases, New Brunswick, New Jersey 08901-1969, United States

Rutgers - New Jersey Medical School CRS, Newark, New Jersey 07103, United States

Jacobi Med. Ctr. Bronx NICHD CRS, Bronx, New York 10461, United States

Columbia IMPAACT CRS, New York, New York 10032, United States

Harlem Hosp. Ctr. NY NICHD CRS, New York, New York 10037, United States

Nyu Ny Nichd Crs, New York, New York 10016, United States

SUNY Stony Brook NICHD CRS, Stony Brook, New York 11794-8111, United States

SUNY Upstate Med. Univ., Dept. of Peds., Syracruse, New York 13210, United States

UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases, Chapel HIll, North Carolina 27599-7220, United States

Oregon Health & Science Univ. - Dept. of Peds., Div. of Infectious Disease, Portland, Oregon 97239, United States

St. Jude/UTHSC CRS, Memphis, Tennessee 38105, United States

Texas Children's Hospital CRS, Houston, Texas 77030, United States

Seattle Children's Hospital CRS, Seattle, Washington 98105, United States

Additional Information

AIDSinfo Drug Database - provides fact sheets on the drugs used in this study.

Click here for more information on starting anti-HIV medications

Click here for more information on HIV regimen failure

Click here for more information on changing regimens

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

Haga clic aquí para ver información sobre este ensayo clínico en español.

Related publications:

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.

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. Review.

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. Review.

McKinney RE Jr, Cunningham CK. Newer treatments for HIV in children. Curr Opin Pediatr. 2004 Feb;16(1):76-9. Review.

Starting date: August 2002
Last updated: November 10, 2014

Page last updated: August 23, 2015

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