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A Study of Ritonavir (an Anti-HIV Drug) in HIV-Positive Infants and Children

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ClinicalTrials.gov Identifier: NCT00000952
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : October 29, 2014
Information provided by (Responsible Party):

Study Description
Brief Summary:

The study examines the safety and effectiveness of ritonavir (an anti-HIV drug), alone and in combination with other anti-HIV drugs, in HIV-positive children under 2 years of age. This study will also determine the most effective doses of ritonavir for future pediatric HIV studies.

Infants infected with HIV by their mothers experience faster disease progression than adults or older children. Treatment with anti-HIV drugs administered at an early age may slow disease progression in infant populations.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Ritonavir Drug: Lamivudine Drug: Zidovudine Phase 1

Detailed Description:

As a group, vertically infected children experience more rapid disease progression than children infected at an older age or adults. The early administration of potent antiretroviral regimens might significantly impact the course of vertical HIV-1 infection.

Infants and children are stratified by age, representative of the developmental differences related to drug metabolism (Group I: at least 6 months - 2 years, Group II: 3-6 months, Group IIIA: 1 month - 10 weeks, IIIB: 1 month - less than 3 months). Within each age group there will be two possible dosage cohorts. All age groups will be enrolled simultaneously into dosage Cohort I, at the initial drug dosage. Progression to Cohort II (at a higher or lower drug dosage) will be decided according to safety, tolerance or viral load in Cohort I. All therapy for Group I/II, whether in Cohort I or II, will be introduced as follows: single dose of ritonavir on Day 0, ritonavir monotherapy through Day 7 AM and combination therapy from Day 7 PM through Week 104. All therapy for Group IIIA & IIIB, whether in Cohort I or II, will be introduced as follows: single dose of ritonavir on Day 0 AM and transition to combination therapy Day 0 PM through Week 104. NOTE: Progression to combination therapy for Group IIIA infants is dependent upon the results of the single-dose ritonavir pharmacokinetics (PK). If the patient is no longer at least presumed to be HIV-infected, he/she will be discontinued from the study. Replacement infants, who will not receive the single dose of ritonavir, will be acquired from Group IIIB infants; new infants that are either presumed HIV infected or have already been shown to be HIV-infected. Clinical evaluations are conducted and blood and urine samples collected regularly during the treatment period in order to quantify HIV-1 levels and determine body chemistries. Pharmacokinetic studies require additional blood sampling up to Week 16. [AS PER AMENDMENT 6/30/98: Pharmacokinetics data from Cohort I showed that the proposed Cohort II starting dose was too low. The dose for Cohort II is now increased. All subjects in Groups I, II, and III will begin combination therapy on Day 0 at the increased dose.] [AS PER AMENDMENT 3/13/00: The study has been extended for an additional 104 weeks, provided the patient's viral load is undetectable (below 400 copies/ml) at the end of the initial study period. While on the treatment extension, patients must continue their current schedule for study drug administration and completion of study visits.]

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Ritonavir Therapy in HIV-1 Infected Infants and Children
Study Completion Date : January 2004

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Ritonavir
U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 2 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

Children may be eligible for this study if they:

  • Are HIV-positive. (Infants under 3 months old presumed to be HIV-positive are eligible to participate in the single-dose phase of the study.)
  • Are between the ages of 4 weeks and 2 years (consent of parent or guardian required).

Exclusion Criteria

Children will not be eligible for this study if they:

  • Have an opportunistic (AIDS-related) infection within 2 months of study entry.
  • Are allergic to 3TC and/or ZDV.
  • Have received anti-HIV drugs for 6 to 12 weeks.
  • Have any infections requiring treatment.
  • Are experiencing wasting (significant weight loss).
  • Have any malignancies (cancer).
  • Have certain immune diseases, are being fed through a tube, or have HIV-related encephalopathy (a degenerative disease of the brain).
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000952

United States, California
Long Beach Memorial Med. Ctr., Miller Children's Hosp.
Long Beach, California, United States, 90806
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States, 92103
United States, District of Columbia
Howard Univ. Washington DC NICHD CRS
Washington, District of Columbia, United States, 20060
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, United States, 02115
United States, New York
NYU Med. Ctr., Dept. of Medicine
New York, New York, United States, 10016
Nyu Ny Nichd Crs
New York, New York, United States, 10016
New York, New York, United States, 10032
Incarnation Children's Ctr.
New York, New York, United States, 10032
Harlem Hosp. Ctr. NY NICHD CRS
New York, New York, United States, 10037
United States, Pennsylvania
The Children's Hosp. of Philadelphia IMPAACT CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Chair: Ram Yogev
Study Chair: Ellen Chadwick
More Information

Scott ZA, Chadwick EG, Catalina MD, McManus M, Yogev R, Palumbo P, Britto P, Sullivan JL, Luzuriaga K. HIV-1-specific CD8+T cells in vertically infected infants: early responses and the effects of antiretroviral therapy. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 169)
Zhao Y, Vetterick T, Lewis D, Yu M, Chadwick E, Yogev R, Coberly SK, Palumbo P. Genotypic mutations in the protease (Pr) and reverse transcriptase (RT) genes associated with antiretroviral resistance to combination therapy with ritonavir/AZT/3TC: a virological sub-study of PACTG 345. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 467)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000952     History of Changes
Other Study ID Numbers: ACTG 345
10602 ( Registry Identifier: DAIDS ES )
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: October 29, 2014
Last Verified: October 2014

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Dose-Response Relationship, Drug
Drug Therapy, Combination
HIV Protease Inhibitors
Anti-HIV Agents

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors