- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00046033
Comparing Standard-Dose Versus Adjusted-Dose Lopinavir/Ritonavir Therapy in HIV-Infected Persons With Drug Resistance
A Phase II, Randomized, Open-Label Study Comparing Fixed-Dose Versus Concentration-Adjusted Lopinavir/Ritonavir Therapy in HIV-Infected Subjects on Salvage Therapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Antiretroviral drugs may fail to suppress HIV unless there are adequate amounts of those drugs in the blood. By monitoring the amounts of drugs in the blood and adjusting doses to achieve optimal drug concentrations, response to antiretroviral drugs may improve, especially in patients who have failed previous regimens. This study is designed to evaluate drug monitoring and dose adjustment of protease inhibitors (PIs) in heavily treatment-experienced patients.
Patients will be randomized to receive either a standard dose of LPV/r (Arm A) or a concentration-adjusted dose of LPV/r (Arm B). Concentration-adjusted dosing means that the dose of ritonavir or lopinavir may be increased based on the amount of lopinavir measured in the blood and the results of a drug resistance test. All patients start the study taking LPV/r, tenofovir disoproxil fumarate (TDF), 0 to 2 additional nucleoside reverse transcriptase inhibitors (NRTIs), and saquinavir (SQV) or amprenavir (APV). Only LPV/r, TDF, and SQV will be provided by the study. Other medications taken as part of the antiretroviral regimen must be obtained outside the study.
Patients in Arm A will take the usual approved dose of LPV/r for the first 24 weeks. At Week 24, patients with high viral loads will come to the clinic for a 12-hour LPV blood level measurement to see if the level of LPV needs to be increased. If it does, an additional capsule of ritonavir will be added to the regimen to boost the level of LPV.
Patients in Arm B will have a series of blood draws over a 12-hour period in the clinic, around 14 days after starting the study, to find out if their LPV level needs to be increased. If the LPV level needs to be raised, an additional capsule of ritonavir will be added to the regimen to boost the level of LPV. Patients who had their ritonavir dose adjusted will return to have another 12-hour blood draw around Week 5. If the LPV level still needs to be changed, an additional capsule of LPV/r will be added to the regimen. A third 12-hour blood draw will be performed around Week 8 if a second dose adjustment was necessary.
During the study, patients will visit the clinic weekly through Week 6, again at Week 8, then every 4 weeks thereafter through Week 32. Patients will have blood drawn at certain visits to test for LPV level, viral load, CD4 count, fasting lipids and glucose, and drug resistance.
Study Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136-1013
- Univ of Miami
-
-
Hawaii
-
Honolulu, Hawaii, United States, 96816-2396
- Univ of Hawaii
-
-
New York
-
New York, New York, United States, 10016
- NYU/Bellevue
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- Case Western Reserve Univ
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15213-2582
- Univ of Pittsburgh
-
-
Texas
-
Galveston, Texas, United States, 77555-0435
- Univ of Texas, Galveston
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- HIV-infection
- Viral load >= 5000 copies/ml within 45 days prior to study entry
- Documented reduction in LPV sensitivity based on results obtained within 45 days prior to study entry
- Prior experience with 2 or more NRTIs for at least 6 months each
- At least 12 weeks of stable antiretroviral treatment that includes at least one PI prior to study entry and may include TDF and/or T-20 for 8 weeks or more immediately prior to study entry
- Negative pregnancy test within 14 days prior to study entry
- Agree not to become pregnant or to impregnate and to use an acceptable form of contraception while receiving study drugs and for 4 weeks after stopping study drugs
Exclusion Criteria:
- Pregnant or breast-feeding.
- Certain drugs within 14 days prior to study entry
- Nonnucleoside reverse transcriptase inhibitors (NNRTIs) within 14 days prior to study entry
- History of intolerance to LPV/r, RTV, or TDF and/or their components
- Drug or alcohol use that, in the opinion of the investigator, would interfere with the study
- Require therapy and/or hospitalization due to a serious infection or medical illness that is potentially life-threatening within 14 days prior to study entry
- Any condition that, in the opinion of the investigator, would compromise ability to participate in the study
- Unexplained fever for 7 consecutive days or chronic diarrhea within 30 days prior to study entry
- Cancer requiring chemotherapy
- Any immune system drugs, HIV vaccine, or other experimental therapy within 30 days prior to study entry
- Plan to use any PI other than APV, SQV, or LPV/r in the initial study treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Collaborators and Investigators
Investigators
- Study Chair: Deborah McMahon, M.D., University of Pittsburgh
Publications and helpful links
General Publications
- Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, Del Giudice P, Montagne N, Schapiro JM, Dellamonica P. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. AIDS. 2000 Jul 7;14(10):1333-9. doi: 10.1097/00002030-200007070-00005.
- Kilby JM, Hill A, Buss N. The effect of ritonavir on saquinavir plasma concentration is independent of ritonavir dosage: combined analysis of pharmacokinetic data from 97 subjects. HIV Med. 2002 Apr;3(2):97-104. doi: 10.1046/j.1468-1293.2002.00090.x.
- Veldkamp AI, van Heeswijk RP, Mulder JW, Meenhorst PL, Schreij G, van der Geest S, Lange JM, Beijnen JH, Hoetelmans RM. Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2001 Aug 1;27(4):344-9. doi: 10.1097/00126334-200108010-00004.
Study record dates
Study Major Dates
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Anti-Bacterial Agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Antitubercular Agents
- Antibiotics, Antitubercular
- Tenofovir
- Ritonavir
- Lopinavir
- Amprenavir
- Saquinavir
Other Study ID Numbers
- ACTG A5135
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infections
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
University of California, San DiegoUniversity of California, Los Angeles; University of Southern California; California... and other collaboratorsCompleted
-
National Institute of Allergy and Infectious Diseases...Eunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedHIV Infections | HIV SeronegativityUnited States, Puerto Rico
-
Erasmus Medical CenterCompletedHIV/AIDS | Opportunistic Infections, HIV RelatedNetherlands
-
Gérond'ifRecruiting
-
University of California, DavisCompleted
-
University of California, San DiegoNational Center for Complementary and Integrative Health (NCCIH)CompletedHIV PositiveUnited States
-
University of ChicagoUniversity of Athens; National Development and Research Institutes, Inc.Completed
-
HIV Prevention Trials NetworkNational Institute on Drug Abuse (NIDA); National Institute of Allergy and...CompletedHIV PositiveIndonesia, Ukraine, Vietnam
-
University of ZimbabweCompleted
Clinical Trials on Ritonavir
-
PfizerNot yet recruitingHealthy Participants | Biological Availability
-
Jiangsu Simcere Pharmaceutical Co., Ltd.Completed
-
Karolinska InstitutetKarolinska University Hospital; PfizerRecruitingCOVID-19 | Post-COVID-19 Syndrome | Long COVID | Long Covid19 | Post COVID-19 Condition | Post-COVID Syndrome | Post COVID-19 Condition, Unspecified | POTS - Postural Orthostatic Tachycardia Syndrome | Postinfectious Inflammation | Postinfectious DisorderSweden
-
Drugs for Neglected DiseasesUniversity of Cape Town; Medecins Sans Frontieres, Netherlands; UBS Optimus Foundation and other collaboratorsCompletedAcquired Immunodeficiency Syndrome | TuberculosisSouth Africa
-
Jiangsu Simcere Pharmaceutical Co., Ltd.Recruiting
-
Fujian Akeylink Biotechnology Co., Ltd.Active, not recruitingCOVID-19 Respiratory InfectionChina
-
Qilu Pharmaceutical Co., Ltd.Recruiting
-
The HIV Netherlands Australia Thailand Research...Ministry of Education, ThailandCompletedHIV Infections | HIV InfectionThailand
-
PfizerCompletedHealthy ParticipantsBelgium