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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2005-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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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 Design

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Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Fosamprenavir

Intervention Type DRUG

Lopinavir/Ritonavir

Intervention Type DRUG

Ritonavir

Intervention Type DRUG

Tenofovir disoproxil fumarate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ann C. Collier, MD

Role: STUDY_CHAIR

University of Washington

Locations

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USC CRS

Los Angeles, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

The Ponce de Leon Ctr. CRS

Atlanta, Georgia, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Indiana Univ. School of Medicine, Wishard Memorial

Indianapolis, Indiana, United States

Site Status

Methodist Hosp. of Indiana

Indianapolis, Indiana, United States

Site Status

HIV Prevention & Treatment CRS

New York, New York, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

MetroHealth CRS

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Vanderbilt Therapeutics CRS

Nashville, Tennessee, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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. doi: 10.1086/375233. Epub 2003 Jun 5.

Reference Type BACKGROUND

PMID: 12802760 (View on PubMed)

Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802. doi: 10.2165/00003495-200363080-00004.

Reference Type BACKGROUND

PMID: 12662125 (View on PubMed)

Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med. 2001 Apr;2(2):105-13. doi: 10.1046/j.1468-1293.2001.00063.x.

Reference Type BACKGROUND

PMID: 11737387 (View on PubMed)

Nadler J. New anti-HIV protease inhibitors provide more treatment options. AIDS Patient Care STDS. 2003 Nov;17(11):551-64. doi: 10.1089/108729103322555944.

Reference Type BACKGROUND

PMID: 14746663 (View on PubMed)

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.

Reference Type BACKGROUND

PMID: 11878403 (View on PubMed)

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. doi: 10.1097/00002030-200501280-00006.

Reference Type RESULT

PMID: 15668539 (View on PubMed)