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

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ClinicalTrials.gov Identifier: NCT00028366

Recruitment Status : Completed

First Posted : December 28, 2001

Last Update Posted : August 16, 2012

Sponsor:

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
HIV Infections	Drug: Fosamprenavir Drug: Lopinavir/Ritonavir Drug: Ritonavir Drug: Tenofovir disoproxil fumarate	Not Applicable

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Enrollment :	56 participants
Intervention Model:	Parallel Assignment
Masking:	None (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
Actual Study Completion Date :	July 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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, 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

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Ann C. Collier, MD	University of Washington

More Information

Publications of Results:

Kashuba AD, Tierney C, Downey GF, Acosta EP, Vergis EN, Klingman K, Mellors JW, Eshleman SH, Scott TR, Collier AC. Combining fosamprenavir with lopinavir/ritonavir substantially reduces amprenavir and lopinavir exposure: ACTG protocol A5143 results. AIDS. 2005 Jan 28;19(2):145-52.

Other Publications:

Cooper CL, van Heeswijk RP, Gallicano K, Cameron DW. A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis. 2003 Jun 15;36(12):1585-92. Epub 2003 Jun 5. Review.

Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802. Review.

Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med. 2001 Apr;2(2):105-13. Review.

Nadler J. New anti-HIV protease inhibitors provide more treatment options. AIDS Patient Care STDS. 2003 Nov;17(11):551-64. Review.

van Heeswijk RP, Veldkamp A, Mulder JW, Meenhorst PL, Lange JM, Beijnen JH, Hoetelmans RM. Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience. Antivir Ther. 2001 Dec;6(4):201-29. Review.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00028366 History of Changes
Other Study ID Numbers:	A5143 10681 ( Registry Identifier: DAIDS ES ) ACTG A5143 AACTG A5143 Substudy AACTG A5147S Substudy ACTG A5147S
First Posted:	December 28, 2001 Key Record Dates
Last Update Posted:	August 16, 2012
Last Verified:	August 2012

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:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir HIV Protease Inhibitors Fosamprenavir	Tenofovir Protease Inhibitors Reverse Transcriptase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Nucleic Acid Synthesis Inhibitors

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