Comparing Standard-Dose Versus Adjusted-Dose Lopinavir/Ritonavir Therapy in HIV-Infected Persons With Drug Resistance

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00046033
First received: September 18, 2002
Last updated: February 28, 2011
Last verified: May 2005
  Purpose

The purpose of this study is to see if adjusting the dose of lopinavir/ritonavir (LPV/r) has a better effect on lowering HIV viral load (the amount of HIV in the blood) compared to taking the standard FDA-approved LPV/r dose. This study will also compare the safety and tolerability of these two types of dosing.


Condition Intervention Phase
HIV Infections
Drug: Lopinavir/ritonavir
Drug: Ritonavir
Drug: Saquinavir
Drug: Tenofovir disoproxil fumarate
Drug: Amprenavir
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


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

Estimated Enrollment: 118
Primary Completion Date: March 2003 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00046033

Locations
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
NYU/Bellevue
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
Sponsors and Collaborators
Investigators
Study Chair: Deborah McMahon, M.D. University of Pittsburgh Division of Infectious Diseases
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00046033     History of Changes
Other Study ID Numbers: ACTG A5135
Study First Received: September 18, 2002
Last Updated: February 28, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Dose-Relationship, Drug
HIV Protease Inhibitors
Salvage Therapy
Viral Load
RNA, Viral
Drug Therapy, Combination

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
HIV Protease Inhibitors
Saquinavir
Ritonavir
Amprenavir
Lopinavir
Tenofovir
Tenofovir disoproxil
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents

ClinicalTrials.gov processed this record on July 20, 2014