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NCT00028366 Clinical Trial

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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT00028366
Other study ID # A5143
Secondary ID 10681ACTG A5143A
Status Completed
Phase N/A
First received
Last updated
Est. completion date July 2005

Study information
Verified date October 2021
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility
Status Completed
Enrollment 56
Est. completion date July 2005
Est. primary completion date
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design

Related Conditions & MeSH terms

Intervention

Drug:
• Fosamprenavir

• Lopinavir/Ritonavir

• Ritonavir

• Tenofovir disoproxil fumarate

Locations
Country Name City State
United States The Ponce de Leon Ctr. CRS Atlanta Georgia
United States Univ. of Cincinnati CRS Cincinnati Ohio
United States Case CRS Cleveland Ohio
United States MetroHealth CRS Cleveland Ohio
United States The Ohio State Univ. AIDS CRS Columbus Ohio
United States Indiana Univ. School of Medicine, Infectious Disease Research Clinic Indianapolis Indiana
United States Indiana Univ. School of Medicine, Wishard Memorial Indianapolis Indiana
United States Methodist Hosp. of Indiana Indianapolis Indiana
United States USC CRS Los Angeles California
United States Vanderbilt Therapeutics CRS Nashville Tennessee
United States HIV Prevention & Treatment CRS New York New York
United States Ucsf Aids Crs San Francisco California
United States University of Washington AIDS CRS Seattle Washington

Sponsors (1)
Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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

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. — View Citation

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

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

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. — View Citation

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