Dual Versus Triple Protease Inhibitor Combinations, Including Ritonavir, in HIV Infected People

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00028366
First received: December 27, 2001
Last updated: August 15, 2012
Last verified: August 2012
  Purpose

Ritonavir (RTV) is a protease inhibitor (PI) commonly used to increase drug levels of other PIs in HIV drug treatment. The purpose of this study is to compare a combination of drugs which includes RTV and 2 protease inhibitors (PIs) with 2 combinations that include RTV and another PI. This study also will compare the effectiveness, safety, tolerability, and drug levels in the blood of these anti-HIV drug combinations.


Condition Intervention
HIV Infections
Drug: Fosamprenavir
Drug: Lopinavir/Ritonavir
Drug: Ritonavir
Drug: Tenofovir disoproxil fumarate

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Comparative Study of Lopinavir/Ritonavir Versus GW433908 and Ritonavir Versus Lopinavir/Ritonavir and GW433908 (In Combination With Tenofovir Disoproxil Fumarate and One or Two Nucleoside Reverse Transcriptase Inhibitors) in HIV-1-Infected Subjects With Virologic Treatment Failure

Resource links provided by NLM:


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

Estimated Enrollment: 56
Study Completion Date: July 2005
Detailed Description:

A substantial proportion of patients on antiretroviral therapy do not achieve sustained suppression of HIV viral load. Developing strategies to improve responses to subsequent regimens is an important objective for the management of patients with HIV infection. Increasing the potency of regimens by using a pharmacoenhancer such as RTV is of interest. RTV is used widely to increase plasma concentrations of PIs, but there is little efficacy and tolerability data about different RTV-enhanced PIs. The efficacy and tolerability of a triple PI regimen will be compared to dual PI regimens; dual PI regimens will also be compared to each other.

In Step 1, patients will be selectively randomized (based on prior exposure to the study drugs) and enrolled into 1 of 3 study arms. Patients in Arm A will receive lopinavir (LPV)/RTV in combination with TDF and 1 or 2 other NRTIs; patients in Arm B will receive fosamprenavir plus RTV in combination with TDF and 1 or 2 other NRTIs; Arm C patients were to receive LPV/RTV plus fosamprenavir in combination with TDF and 1 or 2 other NRTIs. Because interim study results indicated that mean PI levels for patients in Arm C were unacceptably low, Arm C patients will now either drop LPV/RTV and add RTV or drop fosamprenavir from their regimens.

The study will last 24 to 48 weeks. Medications and clinical assessment and blood collection will be performed at 2 weeks prior to entry, entry, and Weeks 2, 4, 8, 12, 16, 24, 32, 40, and 48. Blood samples to test for amprenavir (APV) and LPV pharmacokinetics will be collected at Weeks 12, 24, 48, and at confirmed virologic failure visits. In substudy A5147S, intensive 12-hour pharmacokinetic sampling for APV, LPV, and RTV will be conducted. The first 20-25 patients enrolled in each arm will be enrolled in the substudy 14-28 days after starting study treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Note: Accrual into A5143 and A5147S has been discontinued. The study originally planned to enroll 216 participants, but only 56 participants were enrolled at the time of early termination of enrollment because of interim review results.

Inclusion Criteria for Step 1

  • HIV infected
  • Past anti-HIV therapy consisting of at least 1 PI-containing regimen or detectable viral load, and at least 1 year total anti-HIV therapy experience
  • Viral load of more than 5000 copies/ml within 60 days prior to screening while on a stable anti-HIV therapy for at least 12 weeks
  • Agree to use acceptable forms of contraception

Exclusion Criteria

  • More than 7 days of treatment with LPV and/or more than 7 days of treatment with APV or fosamprenavir
  • HIV vaccine within 90 days of study entry
  • Experimental drugs within 30 days of study entry
  • Cancer chemotherapy within 30 days of study entry
  • Drugs that affect the immune system within 30 days of study entry
  • Certain drugs within 14 days of study entry. Patients who have used drugs that might damage the kidneys within 7 days of study entry are allowed.
  • Midazolam within 7 days of study entry
  • Allergic or sensitive to study drugs
  • Excessive drug or alcohol use
  • Serious illness requiring treatment and/or hospitalization and have not completed therapy, or are not stable on therapy for at least 14 days prior to study entry
  • Pregnant or breastfeeding
  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: NCT00028366

Locations
United States, California
USC CRS
Los Angeles, California, United States, 90033-1079
Ucsf Aids Crs
San Francisco, California, United States, 94110
United States, Georgia
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States, 30308
United States, Indiana
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States, 46202
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States, 46202
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 462025250
United States, New York
HIV Prevention & Treatment CRS
New York, New York, United States
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 452670405
Case CRS
Cleveland, Ohio, United States, 44106
MetroHealth CRS
Cleveland, Ohio, United States, 441091998
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 432101228
United States, Tennessee
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States, 37203
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Ann C. Collier, MD University of Washington
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00028366     History of Changes
Other Study ID Numbers: A5143, 10681, ACTG A5143, AACTG A5143, Substudy AACTG A5147S, Substudy ACTG A5147S
Study First Received: December 27, 2001
Last Updated: August 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Therapy, Combination
HIV Protease Inhibitors
Ritonavir
RNA, Viral
Reverse Transcriptase Inhibitors
Viral Load
ABT 378
tenofovir disoproxil
VX-175
Treatment Experienced

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

ClinicalTrials.gov processed this record on October 23, 2014