Trial record 1 of 1 for:    NCT00118898
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Efavirenz or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir Disoproxil Fumarate or Abacavir/Lamivudine in HIV Infected Treatment-Naive Adults

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00118898
First received: July 7, 2005
Last updated: February 15, 2011
Last verified: February 2011
  Purpose

Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). However, with new anti-HIV drugs being approved, alternative regimens need to be tested to determine if new drug combinations have increased effectiveness in treating HIV. The purpose of this study is to test the safety, tolerability, and effectiveness of four different regimens in HIV-infected adults who have never taken anti-HIV drugs.


Condition Intervention Phase
HIV Infections
Drug: Abacavir/Lamivudine
Drug: Atazanavir
Drug: Efavirenz
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Drug: Ritonavir
Drug: Abacavir/Lamivudine placebo
Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo
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 IIIB, Randomized Trial of Open-Label Efavirenz or Atazanavir With Ritonavir in Combination With Double-Blind Comparison of Emtricitabine/Tenofovir or Abacavir/Lamivudine in Antiretroviral-Naive Subjects

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Time From Randomization to Virologic Failure [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
    Blood samples for determining virologic failure were obtained at visit weeks 16 and 24 , and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks after randomization and before 24 weeks, or >=200 copies/mL at or after 24 weeks. The 5th percentile for time to virologic failure is the time (in weeks) at which 5% of the participants have experienced virologic failure.

  • Time From Treatment Dispensation to a Grade 3/4 Safety Event [ Time Frame: All follow-up while on initially assigned regimen; the median (25th, 75th percentile) follow-up while on initial regimen was 120 (54, 156) weeks and the range was 0 to 205 weeks. ] [ Designated as safety issue: Yes ]
    Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.

  • Time From Treatment Dispensation to Treatment Modification [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
    Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.


Secondary Outcome Measures:
  • Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification) [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
    Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks. Treatment modification was defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.

  • The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Change in CD4 Count (Cells/mm3) From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
    Change was calculated as the CD4 count at Week 48 (or at Week 96) minus the baseline CD4 count (mean of pre-entry and entry values).

  • Number of Participants With Virologic Failure and Emergence of Major Resistance [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: No ]
    Emergence of resistant virus was assessed by genotypic testing performed at Stanford University for all participants who met criteria for virologic failure and retrospectively on baseline samples from these participants. Major mutations were defined by International AIDS Society-United States of America (2008), as well as T69D, L74I, G190C/E/Q/T/V for reverse transcriptase and L24I, F53L, I54V/A/T/S, G73C/S/T/A, N88D for protease.

  • Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. [ Time Frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ] [ Designated as safety issue: Yes ]

    AIDS-defining illnesses were defined per CDC category C definition. HIV-1 related events were defined per CDC category B definition. Events underwent study chair review for classification. See link below for more details.

    http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm


  • Change in Fasting Total Cholesterol Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
    Only fasting results are included. The protocol did not require that samples be collected fasting.

  • Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
    Only fasting results are included. The protocol did not require that samples be collected fasting.

  • Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
    Only fasting results are included. The protocol did not require that samples be collected fasting.

  • Change in Fasting Triglyceride Level From Baseline [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: Yes ]
    Only fasting results are included. The protocol did not require that samples be collected fasting.


Enrollment: 1864
Study Start Date: September 2005
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EFV, FTC/TDF, and placebo ABC/3TC
Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
Drug: Efavirenz
600 mg tablet taken orally daily
Other Name: EFV
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily
Other Name: FTC/TDF
Drug: Abacavir/Lamivudine placebo
Placebo tablet taken orally daily
Other Name: ABC/3TC placebo
Experimental: EFV, ABC/3TC and placebo FTC/TDF
Participants will receive EFV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
Drug: Abacavir/Lamivudine
600 mg abacavir/300 mg lamivudine tablet taken orally daily
Other Name: ABC/3TC
Drug: Efavirenz
600 mg tablet taken orally daily
Other Name: EFV
Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo
Placebo tablet taken orally daily
Other Name: FTC/TDF placebo
Experimental: RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC
Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
Drug: Atazanavir
300 mg tablet taken orally daily
Other Name: ATV
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily
Other Name: FTC/TDF
Drug: Ritonavir
100 mg tablet taken orally daily
Other Name: RTV
Drug: Abacavir/Lamivudine placebo
Placebo tablet taken orally daily
Other Name: ABC/3TC placebo
Experimental: RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF
Participants will receive RTV-boosted ATV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
Drug: Abacavir/Lamivudine
600 mg abacavir/300 mg lamivudine tablet taken orally daily
Other Name: ABC/3TC
Drug: Atazanavir
300 mg tablet taken orally daily
Other Name: ATV
Drug: Ritonavir
100 mg tablet taken orally daily
Other Name: RTV
Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo
Placebo tablet taken orally daily
Other Name: FTC/TDF placebo

Detailed Description:

Antiretroviral (ARV) treatment regimens consisting of EFV and two NRTIs are the most commonly prescribed regimens for the initial therapy of HIV-infected people in the United States. Such regimens are popular because the drugs are easy to administer, have overall excellent efficacy, and are well tolerated. However, because of concerns about long-term drug toxicity, the development of drug resistance, and potential complications in pregnant women, it is imperative that other drug combinations be investigated as possible alternative initial regimens. Drugs recently approved by the Food and Drug Administration (FDA) for HIV treatment include the protease inhibitor (PI) atazanavir (ATV) and the two NRTI coformulations emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and abacavir/lamivudine (ABC/3TC). Data are limited on the efficacy of these new drugs when part of anti-HIV drug regimens. This study will evaluate and compare the safety, tolerability, and efficacy of four different treatment regimens in HIV-infected treatment-naive adults.

The treatment portion of this study will last 96 weeks after the last participant is enrolled. Participants will be randomly assigned to one of four arms:

  • Arm 1 participants will receive EFV, FTC/TDF, and placebo for ABC/3TC.
  • Arm 2 participants will receive EFV, ABC/3TC, and placebo for FTC/TDF.
  • Arm 3 participants will receive ritonavir (RTV)-boosted ATV, FTC/TDF, and placebo for ABC/3TC.
  • Arm 4 participants will receive RTV-boosted ATV, ABC/3TC and placebo for FTC/TDF.

NOTE: Lopinavir/ritonavir may be used in substitution of other drugs for certain participants.

Study visits will occur at study entry; Weeks 1, 2, 4, 8, 16, and 24; and every 12 weeks thereafter. A physical exam, blood collection, and urine collection will occur at most visits. Two pharmacokinetic blood samples will be collected from participants between Weeks 4 and 24. Participants will undergo adherence training at study entry and will be asked to complete adherence questionnaires at selected study visits. Some participants will be asked to participate in ACTG A5224s, a metabolic substudy of ACTG A5202.

The Data Safety Monitoring Board (DSMB) for A5202 met in January 2008 to review the study. After reviewing the study information, the DSMB noted that certain study regimens were significantly less effective than others. Specifically, ABC/3TC-containing regimens were not as effective in controlling the virus as TDF/FTC-containing regimens for participants entering the study with high viral loads. The DSMB also commented that participants assigned to ABC/3TC had a shorter time until they experienced side effects than participants assigned to TDF/FTC. The DSMB had no safety concerns for the other drug comparisons.

Based on DSMB review, in Feb 2008 participants who started the study with high viral loads were told whether they were taking ABC/3TC or TDF/FTC and offered the option to continue or change their NRTI study drug component, after discussion with their doctor. For participants who started the study with lower screening viral loads, study treatment continued without change.

For 74 participant the reason for first treatment modification was "unblinded and switched" as a consequence of the DSMB results (33 on EFV, ABC/3TC, and placebo FTC/TDF arm; 1 on RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC arm; and 40 on RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF arm).

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-infected. A resistance assay must be obtained if the participant has evidence of recent infection. More information on this criterion can be found in the protocol.
  • Antiretroviral naive, defined as 7 days or less of ARV treatment at any time prior to study entry. Participants who have received ARVs as part of postexposure prophylaxis or who have received an investigational drug that was not an NRTI, NNRTI, or PI are eligible for this study.
  • HIV viral load greater than 1,000 copies/ml within 90 days prior to study entry
  • Certain laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the protocol
  • Willing to use acceptable forms of contraception
  • Parent or guardian able and willing to provide written informed consent, if applicable
  • Hepatitis B surface antigen (HBsAg) negative at study entry

Exclusion Criteria:

  • Immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Individuals receiving either stable physiologic glucocorticoid doses, corticosteroids for acute therapy for pneumocystis pneumonia, or a short course (2 weeks or less) of pharmacologic glucocorticoid therapy will not be excluded.
  • Known allergy/sensitivity to study drugs or their formulations
  • Active alcohol or drug use that, in the opinion of the investigator, would interfere with adherence to study requirements
  • Serious illness requiring systemic treatment or hospitalization. Patients who have completed therapy or are clinically stable on therapy for at least 7 days prior to study entry are not excluded.
  • Known clinically relevant cardiac conduction system disease
  • Requirement for any current medications that are prohibited with any study treatment.
  • Evidence of any major drug resistance-associated mutation on any genotype or evidence of significant resistance on any phenotype performed at any time prior to study entry.
  • Current imprisonment or involuntary incarceration for psychiatric or physical (e.g., infectious disease) illness
  • Breastfeeding. Women who become pregnant during the study will be unblinded and required to permanently discontinue their study regimens.
  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: NCT00118898

  Hide Study Locations
Locations
United States, California
Usc Crs (1201)
Los Angeles, California, United States, 90033
UCLA CARE Center CRS (601)
Los Angeles, California, United States, 90035
Stanford CRS (501)
Palo Alto, California, United States, 94304
Ucsd, Avrc Crs (701)
San Diego, California, United States, 92103
Ucsf Aids Crs (801)
San Francisco, California, United States, 94110
San Mateo County AIDS Program (505)
Stanford, California, United States, 94305-5107
Willow Clinic (507)
Stanford, California, United States, 94305-5107
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS (6101)
Aurora, Colorado, United States, 80045
United States, District of Columbia
Georgetown University CRS (GU CRS) (1008)
Washington, District of Columbia, United States, 20007
United States, Florida
University of Miami AIDS CRS (901)
Miami, Florida, United States, 33139
United States, Georgia
The Ponce de Leon Center CRS (5802)
Atlanta, Georgia, United States, 30308
Emory University
Atlanta, Georgia, United States, 30308
United States, Illinois
Cook County Hospital Core Center (2705)
Chicago, Illinois, United States, 60612
Northwestern University CRS (2701)
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS (2702)
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana University Hospital (2601)
Indianapolis, Indiana, United States, 46202-5250
Wishard Hospital (2603)
Indianapolis, Indiana, United States, 46202
United States, Iowa
Univ of Iowa Hosp and Clinic (1504)
Iowa City, Iowa, United States, 52242
United States, Maryland
IHV Baltimore Treatment CRS (4651)
Baltimore, Maryland, United States, 21201
Johns Hopkins Adult AIDS CRS (201)
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess Med. Ctr., ACTG CRS (103)
Boston, Massachusetts, United States, 02215
Bmc Actg Crs (104)
Boston, Massachusetts, United States, 02118
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington U CRS (2101)
St. Louis, Missouri, United States, 63110
United States, New York
SUNY - Buffalo (Rochester) (1102)
Buffalo, New York, United States, 14215
Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)
New York, New York, United States, 10011
HIV Prevention & Treatment CRS (30329)
New York, New York, United States, 10032
Cornell CRS (7804)
New York, New York, United States, 10011
Harlem ACTG CRS (31483)
New York, New York, United States, 10037
NY Univ. HIV/AIDS CRS (401)
New York, New York, United States, 10016
AIDS Community Health Ctr. ACTG CRS (1108)
Rochester, New York, United States, 14604
University of Rochester ACTG CRS (1101)
Rochester, New York, United States, 14642
United States, North Carolina
Wake County Department of Health (30076)
Chapel HIll, North Carolina, United States, 27514
Unc Aids Crs (3201)
Chapel Hill, North Carolina, United States, 27514
Duke University Medical Center Adult CRS (1601)
Durham, North Carolina, United States, 27710
Moses H. Cone Memorial Hospital CRS (3203)
Greensboro, North Carolina, United States, 27401
United States, Ohio
University of Cincinnati CRS (2401)
Cincinnati, Ohio, United States, 45267
Case CRS (2501)
Cleveland, Ohio, United States, 44106
Metro Health CRS (2503)
Cleveland, Ohio, United States, 44109
The Ohio State Univ. AIDS CRS (2301)
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Presbyterian Medical Center - Univ. of PA (6206)
Norristown, Pennsylvania, United States, 19401
Hosp. of the Univ. of Pennsylvania CRS (6201)
Philadelphia, Pennsylvania, United States, 19104
Pitt CRS (1001)
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
The Miriam Hosp. ACTG CRS (2951)
Providence, Rhode Island, United States, 02906
United States, Tennessee
Vanderbilt Therapeutics CRS (3652)
Nashville, Tennessee, United States, 37232
United States, Texas
Peabody Health Center CRS (31443)
Dallas, Texas, United States, 75215
University of Texas, Galveston (6301)
Galveston, Texas, United States, 77555-0435
United States, Washington
University of Washington General Clinical Research (1403)
Seattle, Washington, United States, 98104
University of Washington AIDS CRS (1401)
Seattle, Washington, United States, 98104
Puerto Rico
Puerto Rico-AIDS CRS (5401)
San Juan, Puerto Rico, 00935
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Eric Daar, MD Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute
Study Chair: Paul Sax, MD Division of Infectious Diseases, Brigham and Women's Hospital
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Daniel R. Kuritzkes, M.D., Social & Scientific Systems, Inc.
ClinicalTrials.gov Identifier: NCT00118898     History of Changes
Other Study ID Numbers: ACTG A5202, 1U01AI068636, ACTG 5224s
Study First Received: July 7, 2005
Results First Received: January 8, 2010
Last Updated: February 15, 2011
Health Authority: United States: Federal Government

Keywords provided by AIDS Clinical Trials Group:
Treatment Naive

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
Ritonavir
Atazanavir
Tenofovir
Tenofovir disoproxil
Lamivudine
Abacavir
Efavirenz
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014