Comparing Standard-Dose Versus Adjusted-Dose Lopinavir/Ritonavir Therapy in HIV-Infected Persons With Drug Resistance
Drug: Tenofovir disoproxil fumarate
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II, Randomized, Open-Label Study Comparing Fixed-Dose Versus Concentration-Adjusted Lopinavir/Ritonavir Therapy in HIV-Infected Subjects on Salvage Therapy|
|Primary Completion Date:||March 2003 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00046033
|United States, Florida|
|Univ of Miami|
|Miami, Florida, United States, 33136-1013|
|United States, Hawaii|
|Univ of Hawaii|
|Honolulu, Hawaii, United States, 96816-2396|
|United States, New York|
|New York, New York, United States, 10016|
|United States, Ohio|
|Case Western Reserve Univ|
|Cleveland, Ohio, United States, 44106|
|United States, Pennsylvania|
|Univ of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213-2582|
|United States, Texas|
|Univ of Texas, Galveston|
|Galveston, Texas, United States, 77555-0435|
|Study Chair:||Deborah McMahon, M.D.||University of Pittsburgh Division of Infectious Diseases|