Safety and Effectiveness of Lopinavir/Ritonavir in HIV Infected Infants - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00038480

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Lopinavir/Ritonavir	Phase I

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Lopinavir

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase I/II Study of Lopinavir/Ritonavir in HIV-1 Infected Infants Less Than 6 Months of Age

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Trough concentration of LPV and pharmacokinetic parameters [ Time Frame: Weeks 8, 16, 24, 36, 48, 60, 72, 84, and 96 ]
Recurrent treatment-related Grade 3 and non-life threatening Grade 4 toxicity or single occurence of life-threatening Grade 4 toxicity [ Time Frame: Throughout study ]

Secondary Outcome Measures:

Change in CD4 and CD8 count and percentage from baseline. HIV-1 specific CD4 count and CD8 mediated and humoral responses [ Time Frame: Study entry and Weeks 12, 24, 36, 48, 60, 72, 84, and 96 ]
Time to virologic failure [ Time Frame: Throughout study ]
Suppression of viral load to less than 400 copies/ml and less than 50 copies/ml [ Time Frame: Study entry and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 36, 40, 48, 60, 72, 84, and 96 ]

Estimated Enrollment:	26
Estimated Study Completion Date:	September 2007

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 6 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00038480

Show 32 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Study Chair:	Ellen G. Chadwick, MD	Children's Memorial Hospital, Division of Pediatric Infectious Diseases
Study Chair:	Jorge Pinto, MD, DSc	Escola de Medicine, Universidade Federal de Minas Gerais

More Information

Additional Information:

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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.

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.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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. Epub 2007 Apr 5.

Study ID Numbers:	PACTG P1030
Study First Received:	May 31, 2002
Last Updated:	August 7, 2008
ClinicalTrials.gov Identifier:	NCT00038480 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Lopinavir
HIV-1
Drug Therapy, Combination

HIV Protease Inhibitors
Ritonavir
Reverse Transcriptase Inhibitors

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
HIV Protease Inhibitors
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Protease Inhibitors

Virus Diseases
Lopinavir
Anti-Retroviral Agents
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Retroviridae Infections

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Lopinavir
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
HIV Protease Inhibitors

Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on May 07, 2009