Dual Versus Triple Protease Inhibitor Combinations, Including Ritonavir, in HIV Infected People
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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 |
| Estimated Enrollment: | 56 |
| Study Completion Date: | July 2005 |
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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00028366
| 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, Infectious Disease Research Clinic | |
| Indianapolis, Indiana, United States, 462025250 | |
| Indiana Univ. School of Medicine, Wishard Memorial | |
| Indianapolis, Indiana, United States, 46202 | |
| Methodist Hosp. of Indiana | |
| Indianapolis, Indiana, United States, 46202 | |
| 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 | |
| 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:
|
Lopinavir Protease Inhibitors Reverse Transcriptase Inhibitors Ritonavir Tenofovir Tenofovir disoproxil Anti-HIV Agents Anti-Infective Agents |
Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors HIV Protease Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Therapeutic Uses |
ClinicalTrials.gov processed this record on February 27, 2015