Safety and Effectiveness of Lopinavir/Ritonavir in HIV Infected Infants

NCT ID: NCT00038480

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2007-09-30

Brief Summary

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The purpose of this study is to find out if the drug lopinavir/ritonavir (LPV/RTV) is safe and well tolerated in HIV infected infants. This study will also determine the most effective dose of LPV/RTV for infants.

Detailed Description

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LPV/RTV has shown significant antiviral activity and tolerability in clinical trials in adults and children over 6 months of age. LPV/RTV has been approved by the FDA to treat older children and adults with HIV. Data for children under 6 months, however, have not been available. LPV/RTV has not been approved for infants less than 6 months old, and the appropriate dose for young infants is not known. Dosing guidelines are needed for young infants, most of whom are in the early stages of primary infection. This study will help identify an appropriate dose range of LPV/RTV and evaluate response to therapy in infants less than 6 months of age. The study will also evaluate whether early therapy allows normal development of the immune system.

Infants between 14 days and 6 months of age will receive LPV/RTV in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs) chosen by their physicians. Twelve-hour pharmacokinetic sampling is performed on Day 14 of drug treatment and when the patient reaches 12 months of age. Patients will undergo a physical exam, medical history assessment, and blood collection at selected study visits. Study visits will occur every 2 weeks for the first 8 weeks, then every 4 weeks until the end of the first year of the study. Study visits during the second year will be every 12 weeks until the end of the study. The parent or guardian will be contacted by phone every 6 weeks to monitor adverse drug effects. Participants between the ages of 6 weeks but less than 6 months old will be followed for 96 weeks after the enrollment of the last participant. Participants between the ages of 14 weeks but less than 6 weeks will be followed for 48 weeks after the enrollment of the last participant.

Conditions

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HIV Infections

Keywords

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Lopinavir HIV-1 Drug Therapy, Combination HIV Protease Inhibitors Ritonavir Reverse Transcriptase Inhibitors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Lopinavir/Ritonavir

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV infected
* Viral load greater than 10,000 copies/ml within 30 days prior to study entry
* Weigh more than 5.5 lbs at the time of enrollment
* Agree to take 2 nucleoside reverse transcriptase inhibitors (NRTIs) in addition to LPV/RTV
* Have consent of parent or guardian willing to provide signed informed consent and to have the infant followed at a PACTG site

Exclusion Criteria

* Currently taking a nonnucleoside reverse transcriptase inhibitor or protease inhibitor (PI) while on study
* Previously used LPV/RTV. Patients who were treated previously with other PIs are not excluded. Prior or concurrent maternal treatment with LPV/RTV is not excluded.
* For patients less than 6 weeks old at time of enrollment, less than 34 weeks gestation at delivery OR for patients 6 or more weeks old at time of enrollment, less than 32 weeks gestation at delivery
* Any laboratory toxicity of Grade 3 or greater. Hyperlipasemia of Grade 2 or higher is also excluded.
* Newly diagnosed acute opportunistic or serious bacterial infection requiring therapy at the time of enrollment
* Chemotherapy for active cancer
* Certain medications
* Any other clinically significant conditions, other than HIV infection, that would interfere with the study
Minimum Eligible Age

14 Days

Maximum Eligible Age

6 Months

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

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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Ellen G. Chadwick, MD

Role: STUDY_CHAIR

Children's Memorial Hospital, Division of Pediatric Infectious Diseases

Jorge Pinto, MD, DSc

Role: STUDY_CHAIR

Escola de Medicine, Universidade Federal de Minas Gerais

Locations

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

Oakland, California, United States

Site Status

UCSF Pediatric AIDS CRS

San Francisco, California, United States

Site Status

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States

Site Status

Children's National Med. Ctr. Washington DC NICHD CRS

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

Site Status

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, 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 Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases

Baltimore, Maryland, United States

Site Status

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, United States

Site Status

Baystate Health, Baystate Med. Ctr.

Springfield, Massachusetts, United States

Site Status

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, United States

Site Status

St. Christopher's Hosp. for Children

Philadelphia, Pennsylvania, United States

Site Status

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Site Status

SOM Federal University Minas Gerais Brazil NICHD CRS

Minas Gerais, , Brazil

Site Status

Univ. of Sao Paulo Brazil NICHD CRS

São Paulo, , Brazil

Site Status

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Brazil Puerto Rico

References

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Luzuriaga K, Wu H, McManus M, Britto P, Borkowsky W, Burchett S, Smith B, Mofenson L, Sullivan JL. Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants. J Virol. 1999 Jan;73(1):362-7. doi: 10.1128/JVI.73.1.362-367.1999.

Reference Type BACKGROUND
PMID: 9847340 (View on PubMed)

Equils O, Garratty E, Wei LS, Plaeger S, Tapia M, Deville J, Krogstad P, Sim MS, Nielsen K, Bryson YJ. Recovery of replication-competent virus from CD4 T cell reservoirs and change in coreceptor use in human immunodeficiency virus type 1-infected children responding to highly active antiretroviral therapy. J Infect Dis. 2000 Sep;182(3):751-7. doi: 10.1086/315758. Epub 2000 Aug 15.

Reference Type BACKGROUND
PMID: 10950768 (View on PubMed)

Luzuriaga K, McManus M, Catalina M, Mayack S, Sharkey M, Stevenson M, Sullivan JL. Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses. J Virol. 2000 Aug;74(15):6984-91. doi: 10.1128/jvi.74.15.6984-6991.2000.

Reference Type BACKGROUND
PMID: 10888637 (View on PubMed)

Saez-Llorens X, Violari A, Deetz CO, Rode RA, Gomez P, Handelsman E, Pelton S, Ramilo O, Cahn P, Chadwick E, Allen U, Arpadi S, Castrejon MM, Heuser RS, Kempf DJ, Bertz RJ, Hsu AF, Bernstein B, Renz CL, Sun E. Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2003 Mar;22(3):216-24. doi: 10.1097/01.inf.0000055061.97567.34.

Reference Type BACKGROUND
PMID: 12634581 (View on PubMed)

Chadwick EG, Pinto J, Yogev R, Alvero CG, Hughes MD, Palumbo P, Robbins B, Hazra R, Serchuck L, Heckman BE, Purdue L, Browning R, Luzuriaga K, Rodman J, Capparelli E; International Maternal Pediatric Adolescent Clinical Trials Group (IMPAACT) P1030 Team. Early initiation of lopinavir/ritonavir in infants less than 6 weeks of age: pharmacokinetics and 24-week safety and efficacy. Pediatr Infect Dis J. 2009 Mar;28(3):215-9. doi: 10.1097/INF.0b013e31818cc053.

Reference Type RESULT
PMID: 19209098 (View on PubMed)

Chadwick EG, Yogev R, Alvero CG, Hughes MD, Hazra R, Pinto JA, Robbins BL, Heckman BE, Palumbo PE, Capparelli EV; International Pediatric Adolescent Clinical Trials Group (IMPAACT) P1030 Team. Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir/ritonavir combination antiretroviral therapy. AIDS. 2011 Mar 13;25(5):643-9. doi: 10.1097/QAD.0b013e32834403f6.

Reference Type RESULT
PMID: 21297419 (View on PubMed)

Persaud D, Palumbo PE, Ziemniak C, Hughes MD, Alvero CG, Luzuriaga K, Yogev R, Capparelli EV, Chadwick EG. Dynamics of the resting CD4(+) T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age. AIDS. 2012 Jul 31;26(12):1483-90. doi: 10.1097/QAD.0b013e3283553638.

Reference Type DERIVED
PMID: 22555165 (View on PubMed)

Persaud D, Palumbo P, Ziemniak C, Chen J, Ray SC, Hughes M, Havens P, Purswani M, Gaur AH, Chadwick EG; Pediatric AIDS Clinical Trials Group P1030 Team. Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States. J Infect Dis. 2007 May 15;195(10):1402-10. doi: 10.1086/513871. Epub 2007 Apr 5.

Reference Type DERIVED
PMID: 17436219 (View on PubMed)

Other Identifiers

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10041

Identifier Type: REGISTRY

Identifier Source: secondary_id

PACTG P1030

Identifier Type: -

Identifier Source: secondary_id

P1030

Identifier Type: -

Identifier Source: org_study_id