Comparative Study of Three NNRTI-Sparing HAART Regimens

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Gilead Sciences
Merck Sharp & Dohme Corp.
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00811954
First received: December 18, 2008
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV infected patients who have never received anti-HIV therapy be treated with a triple drug regimen. The most commonly prescribed and successful regimen contains the medication efavirenz (EFV). However, this regimen has been shown to cause undesirable side effects for some patients and is therefore not an option. Alternative regimens are needed for these patients.

This study will look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy. This study will also examine drug tolerability and safety for the various drug combinations.


Condition Intervention Phase
HIV Infection
Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Raltegravir
Drug: Darunavir
Drug: Ritonavir
Drug: Atazanavir
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 Comparative Study of Three Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Sparing Antiretroviral Regimens for Treatment-Naive HIV-1-Infected Volunteers (The ARDENT Study: Atazanavir, Raltegravir, or Darunavir With Emtricitabine/Tenofovir for Naive Treatment)

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Time from virologic failure defined as the time from study entry to the first of two consecutive HIV-1 RNA levels [ Time Frame: At or after Week 16 and before Week 24 or after study Week 24 ] [ Designated as safety issue: No ]
  • Time to discontinuation of the RAL or PI component of randomized treatment for toxicity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Occurrence of new Grade 2, 3, or 4 sign or symptom or Grade 3 or 4 laboratory toxicity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Time to loss of virologic response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Presence of mutations associated with PI, NRTI, or RAL resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Number of drug classes with evidence of resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • CD4 counts and CD4 count changes from baseline [ Time Frame: At Weeks 4, 24, 48, 96, and 144 ] [ Designated as safety issue: No ]
  • Time from study entry to death or AIDS defining condition, or certain targeted serious non-AIDS defining events. See protocol for more detail. [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Targeted serious non-AIDS defining events including CDC category B [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Changes in fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, cardiovascular risk, waist circumference and waist-to-height ratio, and self-reported rates of body shape changes [ Time Frame: At baseline and Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]
  • Self-reported adherence [ Time Frame: At Weeks 4, 24, 48, 96, and 144 ] [ Designated as safety issue: No ]
  • Pregnancy outcomes [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 1813
Study Start Date: May 2009
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Participants will be administered emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily for the entire duration of the study
Drug: Emtricitabine/tenofovir disoproxil fumarate
A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs)
Other Name: TDF/FTC
Drug: Ritonavir
A protease inhibitor (PI)
Other Name: RTV
Drug: Atazanavir
A protease inhibitor (PI)
Other Name: ATZ
Experimental: Group B
Participants will be administered FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily, for the entire duration of the study
Drug: Emtricitabine/tenofovir disoproxil fumarate
A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs)
Other Name: TDF/FTC
Drug: Raltegravir
An integrase inhibitor
Other Name: RAL
Experimental: Group C
Participants will be administered FTC/TDF, darunavir (DRV), and RTV, orally, once daily for the entire duration of the study
Drug: Emtricitabine/tenofovir disoproxil fumarate
A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs)
Other Name: TDF/FTC
Drug: Darunavir
A protease inhibitor (PI)
Other Name: DRV
Drug: Ritonavir
A protease inhibitor (PI)
Other Name: RTV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV infected
  • No evidence of any exclusionary mutations defined as any major NRTI or PI resistance-associated mutation on any genotype or evidence of significant NRTI or PI resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations are not excluded. More information on this criterion can be found in the study protocol.
  • No prior anti-HIV therapy. More information on this criterion can be found in the study protocol.
  • Viral load is 1000 copies/mL or higher, as measured within 90 days prior to study entry
  • Certain laboratory values obtained within 60 days prior to study entry
  • Ability to obtain RTV by prescription
  • Completed cardiovascular risk assessment. More information on this criterion can be found in the study protocol.
  • Must agree to use acceptable forms of contraception while receiving study drugs and for 6 weeks after stopping the medications. More information on this criterion is available in the protocol.
  • Negative pregnancy test within 72 hours before initiating antiretroviral medication
  • Participating in research at any AIDS Clinical Trial Group (ACTG) clinical research site or select International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group sites
  • Ability and willingness of subject or legal guardian/representative to give written informed consent

Exclusion Criteria:

  • Use of immunomodulators, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Those using stable physiologic glucocorticoid doses, a short course of pharmacologic glucocorticoid, corticosteroids for acute therapy treating an opportunistic infection, inhaled or topical corticosteroids, or granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) will not be excluded.
  • Known allergy or sensitivity to study drugs or their ingredients. A history of sulfa allergy is not excluded.
  • Any condition that, in the opinion of the investigator, would compromise the participant's ability to participate in the study
  • Serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 7 days prior to study entry
  • Requirement for any current medications that are prohibited with any study drugs
  • Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness
  • Any prior use of entecavir for treatment of hepatitis B for greater than 8 weeks while the participant was known to be HIV infected
  • Presence of decompensated cirrhosis
  • Pregnant or breastfeeding
  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: NCT00811954

  Show 56 Study Locations
Sponsors and Collaborators
AIDS Clinical Trials Group
Bristol-Myers Squibb
Gilead Sciences
Merck Sharp & Dohme Corp.
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
Study Chair: Jeffrey L. Lennox, MD Emory HIV/AIDS CTU
Study Chair: Judith Silverstein Currier, MD, MSc UCLA AIDS Prevention & Treatment CTU
Principal Investigator: Todd T. Brown, MD, PhD JHU
Principal Investigator: Grace McComsey, MD Case CRS
Principal Investigator: Susan Ellen Cohn, MD, MPH Univ. of Rochester ACTG CRS
  More Information

Additional Information:
Publications:

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00811954     History of Changes
Other Study ID Numbers: ACTG A5257, 1U01AI068636
Study First Received: December 18, 2008
Last Updated: January 28, 2014
Health Authority: United States: Federal Government

Keywords provided by AIDS Clinical Trials Group:
Treatment naive
Treatment inexperienced

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
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Ritonavir
Atazanavir
Darunavir
Emtricitabine
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 22, 2014