A Study on the Management of Combination Anti-HIV Drug Therapy in HIV-Positive Children With Prior Treatment

HIV Infections Clinical Trial

Official title:

RAD-1: A Phase I/II Antiretroviral Management Algorithm for Pediatric Subjects of Four-Drug Combination Therapies Based on Prior Antiretroviral Experience

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000902
• Other study ID #: ACTG 366
• Secondary ID: 11329
• Status: Completed
• Phase: Phase 1
• Est. completion date: April 2002

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the value of changing anti-HIV medications in children with progressive HIV disease who have received previous treatment.

Plasma viral load (the level of HIV in the blood) is probably most effectively reduced by giving patients anti-HIV drugs which affect the virus at various stages of development. Changing the medications may enhance the results of treatment.

Description:

The Master RAD Protocol is based on the concept that optimal suppression of viral load in vivo will be achieved in patients with rapidly progressing or advanced HIV disease (RAD) using antiretroviral combinations inhibiting viral replication at distinct sites of action. Antiretroviral combinations are chosen with the hypothesis that simultaneous change to as many new agents as possible is necessary to maximally reduce plasma viral load.

In this open-label, multicenter study patients are randomized into 1 of 4 groups based on prior antiretroviral experience. Each regimen consists of 4 drugs that include a combination of nucleoside reverse transcriptase inhibitors (stavudine, lamivudine, zidovudine, didanosine, zalcitabine) plus nevirapine (NVP), nelfinavir (NFV), or ritonavir (RTV). Patients must be naive to at least 2 of the 4 drugs in the regimen and at least 1 of the novel drugs must be NVP, NFV, or RTV.

Prior to randomization to a NFV- or RTV-containing regimen, patients are stratified by HIV RNA (greater than or equal to 50,000 or less than 50,000) and must able to receive 2 or more novel drugs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: April 2002
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 21 Years

Eligibility

Inclusion Criteria

Your child may be eligible for this study if he or she:

• Is HIV-positive.

• Is between the ages of 6 months and 21 years (consent of parent or guardian required if under 18).

• Has an HIV blood level above 50,000 copies/mL on 2 consecutive occasions, while taking anti-HIV therapy.

• Has advanced HIV disease or disease progression while receiving 8 weeks or more of continuous unchanged anti-HIV therapy.

• Is able to receive at least one of the following: RTV, NVP, or NFV.

Exclusion Criteria

Your child will not be eligible for this study if he or she:

• Is receiving treatment for a serious bacterial, viral, or opportunistic (HIV-associated) infection within 14 days prior to study entry.

• Has a history of pancreatitis or peripheral neuropathy.

• Has cancer requiring chemotherapy.

• Is allergic to the study medications.

• Is taking certain medications.

• Is pregnant.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Ritonavir

• Nelfinavir mesylate

• Nevirapine

• Lamivudine

• Stavudine

• Zidovudine

• Zalcitabine

• Didanosine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
United States	Children's Hosp at Albany Med Ctr	Albany	New York
United States	Emory Univ Hosp / Pediatrics	Atlanta	Georgia
United States	Med College of Georgia	Augusta	Georgia
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Univ of Alabama at Birmingham - Pediatric	Birmingham	Alabama
United States	Boston City Hosp / Pediatrics	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	SUNY - Brooklyn	Brooklyn	New York
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	Columbus Children's Hosp	Columbus	Ohio
United States	The Med Ctr Inc	Columbus	Georgia
United States	Children's Med Ctr of Dallas	Dallas	Texas
United States	Children's Hosp of Denver	Denver	Colorado
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr	Durham	North Carolina
United States	Connecticut Children's Med Ctr	Farmington	Connecticut
United States	North Broward Hosp District	Fort Lauderdale	Florida
United States	North Shore Univ Hosp	Great Neck	New York
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	Univ of Mississippi Med Ctr	Jackson	Mississippi
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California
United States	Long Beach Memorial (Pediatric)	Long Beach	California
United States	Cedars Sinai / UCLA Med Ctr	Los Angeles	California
United States	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	Saint Jude Children's Research Hosp of Memphis	Memphis	Tennessee
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Univ of South Alabama	Mobile	Alabama
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
United States	UMDNJ - Robert Wood Johnson Med School / Pediatrics	New Brunswick	New Jersey
United States	Yale Univ Med School	New Haven	Connecticut
United States	Schneider Children's Hosp	New Hyde Park	New York
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Cornell Univ Med College	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Incarnation Children's Ctr / Columbia Presbyterian Med Ctr	New York	New York
United States	Metropolitan Hosp Ctr	New York	New York
United States	Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	Children's Hosp of the King's Daughters	Norfolk	Virginia
United States	Children's Hosp of Oakland	Oakland	California
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania
United States	Med College of Virginia	Richmond	Virginia
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	State Univ of New York at Stony Brook	Stony Brook	New York
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Univ of Massachusetts Med School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (7)

EV Capparelli, SK Burchett, A Kovacs, M Khoury, R Oyomopito, L Mofenson, B Zimmer, D Holland. Characterization of the Ritonavir-Nelfinavir Pharmacokinetic Interaction in Pediatric Patients with Advanced HIV Disease Using a Mixed Effects Modeling Approach,

Frenkel LM, Burchett SK, Aldrovandi GM, Carey V, Oyomopito R, Mahalanibis M, Decker D, Kovacs A. HIV-1 reverse transcriptase (RT) M184V/I improves the rate of suppression of viral replication by salvage therapy. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 463)

Kovacs A, Burchett S, Khoury M, Carey V, Pahwa S, McIntosh K, Oyomopito R, Smith E, Mofenson L. Virologic and immunologic responses in children with advanced HIV disease on a new HAART regimen (PACTG 366). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 684)

S. Burchett, M. Khoury, K. McIntosh, V. Carey, R. Oyomopito, L. Mofenson, E. Smith, A. Kovacs, Viral Load Reduction in Children with Advanced HIV Disease Treated with 4-Drug Antiretroviral Treatment Regimens Including NRTIs, Nevirapine, Nelfinavir and/or

Saitoh A, Sarles E, Capparelli E, Aweeka F, Kovacs A, Burchett SK, Wiznia A, Nachman S, Fenton T, Spector SA. CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. AIDS. 2007 Oct 18;21(16 — View Citation

Weinberg A, Kovacs A, Pahwa S, Carey V, Oyomopito R, Mofenson L, Khoury M, Zimmer B, Burchett S. HIV-infected children on HAART reconstitute tetanus-specific T cell responses without booster vaccination. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 688)

Weinberg A, Pahwa S, Oyomopito R, Carey VJ, Zimmer B, Mofenson L, Kovacs A, Burchett SK; Pediatric AIDS Clinical Trials Group 366 Team. Antimicrobial-specific cell-mediated immune reconstitution in children with advanced human immunodeficiency virus infection receiving highly active antiretroviral therapy. Clin Infect Dis. 2004 Jul 1;39(1):107-14. Epub 2004 Jun 14. — View Citation