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



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

For Condition: HIV Infections
Status: No longer recruiting
Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) ,
Synopsis: 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.
Details: 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:
Study Type:
  Interventional, Treatment, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Minimum Age/Maximum Age: 18 Years/
Genders: Both
Protocol Entry 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
Total Enrollment: 56

Location and Contact Information:

Overall Study Official:
AnnCollier,  Study Chair,  University of Washington Harborview Medical Center

Univ of Southern California / LA County USC Med Ctr
Los Angeles,  California,  90033-1079
United States
 

Philadelphia Veterans Administration Med Ctr
Philadelphia,  Pennsylvania,  19104
United States
 

Univ of North Carolina
Chapel Hill,  North Carolina,  275997215
United States
 

Indiana Univ Hosp
Indianapolis,  Indiana,  462025250
United States
 

Brigham and Women's Hosp
Boston,  Massachusetts,  02215
United States
 

Comprehensive Care Clinic
Nashville,  Tennessee,  37203
United States
 

Columbia Presbyterian Med Ctr
New York City,  New York,  10032
United States
 

Cornell Univ Med Ctr
New York City,  New York,  10021
United States
 

Univ of California San Francisco
San Francisco,  California,  94110
United States
 

Methodist Hosp of Indiana / Life Care Clinic
Indianapolis,  Indiana,  46202
United States
 

Beth Israel Med Ctr
New York City,  New York,  10003
United States
 

MetroHealth Med Ctr
Cleveland,  Ohio,  441091998
United States
 

Stanford Univ Med Ctr
Stanford,  California,  943055107
United States
 

Univ of Texas, Southwestern Med Ctr
Dallas,  Texas,  75235-9173
United States
 

Rush Presbyterian - Saint Luke's Med Ctr
Chicago,  Illinois,  60612
United States
 

Wishard Hosp
Indianapolis,  Indiana,  46202
United States
 

Case Western Reserve Univ
Cleveland,  Ohio,  44106
United States
 

Emory Univ
Atlanta,  Georgia,  30308
United States
 

Beth Israel Deaconess - West Campus
Boston,  Massachusetts,  02215
United States
 

Cornell Clinical Trials Unit - Chelsea Clinic
New York City,  New York,  10011
United States
 

Univ of Miami School of Medicine
Miami,  Florida,  331361013
United States
 

Northwestern Univ Med School
Chicago,  Illinois,  60611
United States
 

Univ of Colorado Health Sciences Ctr
Denver,  Colorado,  80262
United States
 

Bellevue Hosp / New York Univ Med Ctr
New York City,  New York,  10016
United States
 

Cleveland Clinic
Cleveland,  Ohio,  44106-5083
United States
 

Univ of Pittsburgh
Pittsburgh,  Pennsylvania,  15213-2582
United States
 

Univ of Pennsylvania
Philadelphia,  Pennsylvania,  19104
United States
 

Willow Clinic
Menlo Park,  California,  94025
United States
 

Harvard (Massachusetts Gen Hosp)
Boston,  Massachusetts,  02114
United States
 

Univ of Washington
Seattle,  Washington,  98104
United States
 

Ohio State Univ Hosp Clinic
Columbus,  Ohio,  432101228
United States
 

Univ of Cincinnati
Cincinnati,  Ohio,  452670405
United States
 

San Mateo AIDS Program / Stanford Univ
Stanford,  California,  943055107
United States
 

Harbor UCLA Med Ctr
Torrance,  California,  90502
United States
 

Univ of Texas, Galveston
Galveston,  Texas,  77555-0435
United States
 

The CORE Ctr
Chicago,  Illinois,  60612
United States
 

Boston Med Ctr
Boston,  Massachusetts,  02118
United States
 


Additional Information:
Study ID Numbers:
  ACTG A5143;  Substudy AACTG A5147S,Substudy ACTG A5147S,AACTG A5143
Study Start Date: 
Record last reviewed: May 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00028366

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