Dual Versus Triple Protease Inhibitor Combinations, Including Ritonavir, in HIV Infected People - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00028366

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:	Treatment, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Ritonavir Lopinavir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Fosamprenavir Fosamprenavir sodium Fosamprenavir calcium

U.S. FDA Resources

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

Estimated Enrollment:

56

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00028366

Show 37 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Ann C. Collier, MD

University of Washington Harborview Medical Center

More Information

Additional Information:

Click here for more information about fosamprenavir This link exits the ClinicalTrials.gov site

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Click here for more information about ritonavir This link exits the ClinicalTrials.gov site

Click here for more information about tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

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.

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 05. 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.

Study ID Numbers:	ACTG A5143, AACTG A5143, Substudy AACTG A5147S, Substudy ACTG A5147S
Study First Received:	December 27, 2001
Last Updated:	August 25, 2008
ClinicalTrials.gov Identifier:	NCT00028366 History of Changes
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

Study placed in the following topic categories:

HIV Protease Inhibitors
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Protease Inhibitors
Reverse Transcriptase Inhibitors
Virus Diseases

Anti-Retroviral Agents
Lopinavir
Fosamprenavir
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Lopinavir
Anti-Retroviral Agents
Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil
HIV Protease Inhibitors
RNA Virus Infections

Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
Fosamprenavir
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on July 02, 2009