Safety of Saquinavir and High Doses of Lopinavir/Ritonavir in Children With HIV
A Phase I/II Safety, Tolerability, and Pharmacokinetic Study of High Dose Lopinavir/Ritonavir With or Without Saquinavir in HIV-Infected Pediatric Subjects Previously Treated With Protease Inhibitors
3 other identifiers
interventional
26
2 countries
15
Brief Summary
The purpose of this study is to determine the effect of increased doses of lopinavir/ritonavir (LPV/r) and saquinavir (SQV) in HIV infected children who are failing their current antiretroviral regimen
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 hiv-infections
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 4, 2004
CompletedFirst Posted
Study publicly available on registry
June 7, 2004
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2006
CompletedNovember 1, 2021
October 1, 2021
June 4, 2004
October 28, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Life-threatening adverse events attributable to study drugs
dose-limiting toxicity, defined as adverse events of Grade 3 or greater attributable to study drug and require dose reduction or interruption but are not judged to be life-threatening by the protocol team
Secondary Outcomes (5)
Pharmacological success, defined as achieving an inhibitory quotient (IQ) of 15 after 2 weeks on high-dose LPV/r without life-threatening or dose-limiting toxicity
virologic success, defined by optimal response (undetectable viral load) at Week 24 or adequate response (0.75 log drop in viral load or more) from baseline to Week 24
immunologic success, defined as a CD4% increase from baseline of 5% or more points by Week 24
minimal criterion for overall success, defined as a 0.75 log drop in viral load or more or 5% point increase in CD4% from baseline to Week 24
virologic failure, defined as an inadequate (less than 0.75 log drop in viral load) or suboptimal (confirmed viral load of greater than 400 copies/ml) response at Week 24
Interventions
Eligibility Criteria
You may qualify if:
- HIV infected
- HIV RNA viral load greater than 5,000 copies/ml
- At least 6 months of continuous therapy with a protease inhibitor (PI) prior to study entry
- No change in antiretroviral therapy since genotypic resistance testing
- Genotypic resistance testing indicating a primary protease mutation at position 32, 47, 48, 50, 82, or 84 and at least three other mutations in positions 10, 20, 24, 30, 32, 33, 36, 46, 47, 48, 50, 53, 54, 71, 73, 77, 82, 84, or 90 OR phenotypic resistance testing, within 6 months of screening while on a failing regimen, indicating at least a fivefold increase in LPV as compared to wild type HIV
- Parent or legal guardian willing to provide informed consent
- If sexually active, agree to use acceptable methods of contraception
- Have a telephone, pager, or other method of reliable communication with study staff
- Able and willing to swallow study medications
You may not qualify if:
- Any drug toxicity greater than Grade 3 at screening
- Certain abnormal laboratory values
- Acute opportunistic or serious bacterial infection requiring treatment
- Chemotherapy for active cancer
- Any significant diseases (other than HIV infection) that may, in the opinion of the investigator, interfere with the study
- Require certain medications
- History of heart problems
- Family history of prolonged QTc-Interval Syndrome or prolonged QTc-interval at study entry
- Pregnancy or breastfeeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
UAB, Dept. of Ped., Div. of Infectious Diseases
Birmingham, Alabama, 35233, United States
Long Beach Memorial Med. Ctr., Miller Children's Hosp.
Long Beach, California, 90801, United States
UCSF Pediatric AIDS CRS
San Francisco, California, 94143-0105, United States
Chicago Children's CRS
Chicago, Illinois, 60614, United States
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, 70112-2699, United States
Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
Baltimore, Maryland, United States
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, United States
Harlem Hosp. Ctr. NY NICHD CRS
New York, New York, 10037, United States
Nyu Ny Nichd Crs
New York, New York, United States
Strong Memorial Hospital Rochester NY NICHD CRS
Rochester, New York, 14642-0001, United States
Jacobi Med. Ctr.
The Bronx, New York, 10461, United States
DUMC Ped. CRS
Durham, North Carolina, 27705, United States
St. Jude/UTHSC CRS
Memphis, Tennessee, 38105-2794, United States
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
San Juan, 00936-5067, Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico
Related Publications (6)
Foster C, Lyall EG. Children with HIV: improved mortality and morbidity with combination antiretroviral therapy. Curr Opin Infect Dis. 2005 Jun;18(3):253-9. doi: 10.1097/01.qco.0000168387.24142.cf.
PMID: 15864104BACKGROUNDHavlir DV, Gilbert PB, Bennett K, Collier AC, Hirsch MS, Tebas P, Adams EM, Wheat LJ, Goodwin D, Schnittman S, Holohan MK, Richman DD; ACTG 5025 Study Group. Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression. AIDS. 2001 Jul 27;15(11):1379-88. doi: 10.1097/00002030-200107270-00007.
PMID: 11504959BACKGROUNDKempf DJ, Isaacson JD, King MS, Brun SC, Sylte J, Richards B, Bernstein B, Rode R, Sun E. Analysis of the virological response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1-infected patients receiving lopinavir/ritonavir therapy. Antivir Ther. 2002 Sep;7(3):165-74.
PMID: 12487383BACKGROUNDKulkosky J, Nunnari G, Otero M, Calarota S, Dornadula G, Zhang H, Malin A, Sullivan J, Xu Y, DeSimone J, Babinchak T, Stern J, Cavert W, Haase A, Pomerantz RJ. Intensification and stimulation therapy for human immunodeficiency virus type 1 reservoirs in infected persons receiving virally suppressive highly active antiretroviral therapy. J Infect Dis. 2002 Nov 15;186(10):1403-11. doi: 10.1086/344357. Epub 2002 Oct 29.
PMID: 12404155BACKGROUNDMalee K, Williams PL, Montepiedra G, Nichols S, Sirois PA, Storm D, Farley J, Kammerer B; PACTG 219C Team. The role of cognitive functioning in medication adherence of children and adolescents with HIV infection. J Pediatr Psychol. 2009 Mar;34(2):164-75. doi: 10.1093/jpepsy/jsn068. Epub 2008 Jul 22.
PMID: 18647794RESULTRobbins BL, Capparelli EV, Chadwick EG, Yogev R, Serchuck L, Worrell C, Smith ME, Alvero C, Fenton T, Heckman B, Pelton SI, Aldrovandi G, Borkowsky W, Rodman J, Havens PL; PACTG 1038 Team. Pharmacokinetics of high-dose lopinavir-ritonavir with and without saquinavir or nonnucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected pediatric and adolescent patients previously treated with protease inhibitors. Antimicrob Agents Chemother. 2008 Sep;52(9):3276-83. doi: 10.1128/AAC.00224-08. Epub 2008 Jul 14.
PMID: 18625762RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Peter L. Havens, MD
Medical College of Wisconsin
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 4, 2004
First Posted
June 7, 2004
Study Completion
December 1, 2006
Last Updated
November 1, 2021
Record last verified: 2021-10