Comparing the Safety, Effectiveness, and Tolerability of Three Anti-HIV Drug Regimens for Treatment-Naive Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00050895
First received: December 30, 2002
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

With new strategies and drugs available, many different regimens exist for the treatment of HIV. The purpose of this study is to compare three different anti-HIV drug regimens as first-time treatments for HIV infection.


Condition Intervention Phase
HIV Infections
Drug: Lopinavir/ritonavir
Drug: Efavirenz
Drug: Stavudine
Drug: Zidovudine
Drug: Lamivudine
Drug: Tenofovir disoproxil fumarate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Open-Label Comparison of Lopinavir/Ritonavir Plus Efavirenz Versus Lopinavir/Ritonavir Plus 2 NRTIs Versus Efavirenz Plus 2 NRTIs as Initial Therapy for HIV-1 Infection

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time from study entry to virologic failure
  • time from study entry to regimen completion

Secondary Outcome Measures:
  • 20 % or more loss in peripheral fat
  • increase in lactic acid levels at least 2-4old above the upper limit of normal (ULN)
  • 20 % or more increase in truncal fat accumulation
  • fasting cholesterol level equal to or greater than 240 mg/dl
  • Grade 3 or greater elevation in fasting triglyceride levels
  • change from baseline in insulin resistance [ Time Frame: at Weeks 24, 48 and 96 ]
  • change from baseline of whole-body bone density and whole-body bone mineral content [ Time Frame: at Weeks 48 and 96 ]
  • time to confirmed virologic failure while on Steps I (initial randomized regimen) or II (within class substitutes for initial regimen toxicity) OR treatment-limiting toxicity on Steps I or II
  • number of antiretroviral classes with resistance mutations at virologic failure
  • number of missed medication doses [ Time Frame: 4 days prior ]
  • change from baseline in self-reported symptoms OR occurrence of reporting an increase in symptoms [ Time Frame: at Weeks 4, 48, 72 and 96 ]
  • change from baseline in body image OR occurrence of reporting body image distress [ Time Frame: at Weeks 24, 48, 72 and 96 ]
  • time until treatment-limiting toxicity OR occurrence of Grades 3 or 4 toxicity

Estimated Enrollment: 775
Study Completion Date: March 2006
Detailed Description:

Numerous treatment options are available to HIV infected patients who are antiretroviral (ARV) therapy naive, but an optimal regimen has not yet been established. This study will compare a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, a ritonavir (RTV)-enhanced protease inhibitor (PI)-based regimen, and a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen for the initial treatment of HIV infection.

Patients will be randomly assigned to one of three study arms. In Arm A, patients will receive lopinavir/ritonavir (LPV/r) twice daily and efavirenz (EFV) once daily before bed. Arm B patients will receive LPV/r twice daily, lamivudine (3TC) once daily, plus either stavudine extended release (d4T XR) once daily, zidovudine (ZDV) twice daily, or tenofovir disoproxil fumarate (TDF) once daily. Patients in Arm C will receive EFV once daily before bed and 3TC plus either d4T XR once daily before bed, ZDV twice daily, or TDF once daily before bed.

Study visits will occur every 4 weeks until Week 24, then every 8 weeks thereafter for a maximum of 96 weeks. Blood will be drawn at every visit and a urine sample will be collected every 8 weeks. Body measurements will be taken at Weeks 24, 48, 72, and 96. Whole body dual-energy x-ray absorptiometry (DEXA) scans will be done at Weeks 48 and 96. Patients must fast before study visits at Weeks 12, 24, 48, 72, and 96. Women in the study will have gynecological assessments every 24 weeks.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Step 1:

  • HIV infected
  • HIV viral load of 2000 copies/ml or greater within 60 days prior to study entry
  • Willing to use acceptable means of contraception
  • d4T XR, TDF, or ZDV chosen as part of an initial regimen prior to randomization to a study arm
  • Coenrolled in ACTG A5152s

Exclusion Criteria for Step 1:

  • On ARV therapy for 7 days or more any time prior to study entry
  • NNRTIs or 3TC at any time prior to study entry
  • Current peripheral neuropathy of Grade 2 or higher
  • Pregnancy or breastfeeding
  • Immunomodulators, vaccines, or investigational therapies within 30 days of study entry. Patients taking a stable or tapering dose of prednisone at less than 10 mg are not excluded.
  • Human growth hormone within 30 days prior to study entry
  • Initiation of testosterone or anabolic steroids within 30 days prior to study entry
  • Certain other medications within 30 days of study entry
  • Hypersensitivity to components of the study drug formulations
  • Drug or alcohol use or dependence that would interfere with adherence to study requirements
  • Acute therapy for serious medical illnesses requiring systemic treatment and/or hospitalization within 14 days prior to study entry
  • Recent infection with drug-resistant HIV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00050895

  Hide Study Locations
Locations
United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States, 35924
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095-1793
USC CRS
Los Angeles, California, United States, 90033-1079
Stanford CRS
Palo Alto, California, United States, 94305-5107
UC Davis Medical Center
Sacramento, California, United States, 95814
Univ. of California Davis Med. Ctr., ACTU
Sacramento, California, United States
Ucsd, Avrc Crs
San Diego, California, United States, 92103
Ucsf Aids Crs
San Francisco, California, United States, 94110
Santa Clara Valley Med. Ctr.
San Jose, California, United States, 94305-5107
San Mateo County AIDS Program
San Mateo, California, United States, 94305-5107
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502-2052
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262-3706
United States, District of Columbia
Georgetown University CRS (GU CRS)
Washington, District of Columbia, United States, 20007
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Georgia
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States, 30308
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Illinois
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612-3806
Northwestern University CRS
Chicago, Illinois, United States, 60611-3015
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202-5250
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States, 46202-1261
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States, 46202
United States, Iowa
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States, 52242-1201
United States, Maryland
IHV Baltimore Treatment CRS
Baltimore, Maryland, United States, 21201
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
SSTAR, Family Healthcare Ctr.
Fall River, Massachusetts, United States
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455-0392
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States, 63108-2138
St. Louis ConnectCare, Infectious Diseases Clinic
St. Louis, Missouri, United States, 63108-2138
United States, Nebraska
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, United States, 68198-5130
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
Cornell CRS
New York, New York, United States, 10021
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016-6481
Columbia Univ., HIV Prevention and Treatment Medical Ctr.
New York, New York, United States, 10032-3784
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
HIV Prevention & Treatment CRS
New York, New York, United States
Weill Med. College of Cornell Univ., The Cornell CTU
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642-0001
AIDS Care CRS
Rochester, New York, United States
McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit
Rochester, New York, United States
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27514
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
Wake County Health and Human Services CRS
Raleigh, North Carolina, United States
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267-0405
MetroHealth CRS
Cleveland, Ohio, United States, 44109-1998
Case CRS
Cleveland, Ohio, United States, 44106-5083
Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases
Cleveland, Ohio, United States, 44109-5083
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 43210-1282
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19401
Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
Philadelphia, Pennsylvania, United States, 19104
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213-2582
United States, Rhode Island
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, United States, 02906
Rhode Island Hosp.
Providence, Rhode Island, United States, 02906
United States, Tennessee
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States, 37203
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
South Africa
Durban Adult HIV CRS
Durban, KwaZulu-Natal, South Africa
Sponsors and Collaborators
Investigators
Study Chair: Sharon Riddler, MD University of Pittsburgh Division of Infectious Diseases
Study Chair: Richard Haubrich, MD University of California, San Diego, Division of Infectious Diseases
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00050895     History of Changes
Other Study ID Numbers: A5142, 10085, ACTG A5142, A5152s, A5160s
Study First Received: December 30, 2002
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Reverse Transcriptase Inhibitors
HIV Protease Inhibitors
Drug Therapy, Combination
Delayed Action Preparations
Treatment Naive
HIV-1

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Stavudine
Lamivudine
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Efavirenz
Ritonavir
Lopinavir
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014