ALTAIR - Alternative Antiretroviral Strategies : a Comparison of Three Initial Regimens

This study has been completed.
Sponsor:
Collaborator:
The University of New South Wales
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00335322
First received: June 8, 2006
Last updated: April 17, 2012
Last verified: April 2012
  Purpose

In treatment naïve HIV infected subjects, combination antiretroviral therapy including efavirenz combined with tenofovir and emtricitabine will offer non-inferior antiretroviral efficacy over 48 weeks, compared to either atazanavir boosted with ritonavir combined with tenofovir and emtricitabine or tenofovir and emtricitabine combined with zidovudine and abacavir, as assessed by change from baseline plasma HIV-1 RNA viral load.


Condition Intervention Phase
Human Immunodeficiency Virus (HIV)
Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin (efavirenz)
Drug: Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV)
Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)
Phase 4

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 Randomised, Open-label, 96-week Study Comparing the Safety and Efficacy of Three Different Combination Antiretroviral Regimens as Initial Therapy for HIV Infection.

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • Time-weighted Mean Change From Baseline Plasma HIV-RNA. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare the Safety of Three Strategic Regimens of Initial ART Containing a Fixed Dose Formulation of Tenofovir and Emtricitabine, With Either Efavirenz or Ritonavir Boosted Atazanavir or Zidovudine Plus Abacavir. [ Time Frame: 144 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 329
Study Start Date: February 2007
Study Completion Date: November 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin efavirenz)
Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + Stocrin (efavirenz)
Truvada (tenofovir 300mg qd + 200mg qd) once daily Efavirenz 600mg qd once daily
Active Comparator: 2
Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV)
Drug: Truvada (fixed dose combination of tenofovir + emtricitabine)+ ritonavir/atazanavir (r/ATV)
Tuvada (tenofovir 300mg qd + 200mg qd) once daily ritoanvir/atazanavir 100mg/300mg qd once daily (taken with food)
Experimental: 3
Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)
Drug: Truvada (fixed dose combination of tenofovir + emtricitabine) + zidovudine (ZDV) + abacavir (ABC)
Tuvada (tenofovir 300mg qd + 200mg qd) once daily zidovudine 250mg/300mg qd (taken in two equal doses approximately 12 hours apart) Abacavir 600mg qd

Detailed Description:

The primary objective of this study is to compare the virological efficacy, as measured by the time-weighted mean change from baseline plasma HIV-RNA, and safety, of three strategic regimens of initial antiretroviral therapy (ART) containing a fixed dose formulation of tenofovir and emtricitabine, with either efavirenz or ritonavir boosted atazanavir or zidovudine plus abacavir. (Primary comparisons are regimen I versus II and I versus III as described below).

I. tenofovir (TDF) + emtricitabine (FTC) + efavirenz (EFV) II. tenofovir (TDF) + emtricitabine (FTC) + ritonavir/atazanavir (r/ATV) III. tenofovir (TDF) + emtricitabine (FTC) + zidovudine (ZDV) + abacavir (ABC)

Secondary objectives of this study will be to undertake a range of analyses including but not limited to the following,

  1. Percentage of patients < 50 copies HIV RNA/mL (and < 400 copies/mL) at week 48 and week 96 between treatment arms.
  2. Time to confirmed (first of two consecutive) plasma HIV-1 RNA < 50 copies/mL (and < 400 copies/mL) between treatment arms.
  3. Time to virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL (and 400 copies/mL) after confirmed < 50 copies/mL (where time = 0 if patient never achieves plasma virus load < 50 or <400 copies/mL).
  4. Mean change from baseline of absolute CD4+ T cell count at weeks 48 and 96 between treatment arms.
  5. Time to change in randomly assigned therapy (all reasons individually and on aggregate) between treatment arms.
  6. Time to first virologic failure (defined as #3 above) or cessation of randomly assigned antiretroviral therapy.
  7. Mean change from baseline Lipodystrophy Case Definition score at weeks 48 and 96 between treatment arms.
  8. Mean change from baseline in peripheral and central adipose tissue, as measured by CT and DEXA at weeks 48 and 96 between treatment arms.
  9. Mean change from baseline in fasting lipid and glycemic parameters at weeks 48 and 96 between treatment arms.
  10. Comparison of total number of patients with any serious adverse events (SAEs), and the cumulative incidence of SAEs, between treatment arms.
  11. Comparison of total number of patients with any adverse events (AEs), and the cumulative incidence of AEs, associated with cessation of randomly assigned therapy between treatment arms.
  12. Patterns of genotypic HIV resistance associated with virological treatment failure across treatment arms.
  13. Describe aspects of immune reconstitution disease.
  14. Adherence to therapy and associations with virologic outcomes between treatment arms.
  15. Comparison of quality of life between treatment arms.

Following the result of the scheduled week 48 data analysis, the protocol steering committee amended the study protocol as follows:

  • Patients on Arms I and II will remain on the current study drugs
  • Patients on Arm III may be switched at the physician's discretion to either Arm I or II
  • There will be a protocol amendment to include one extra follow up visit at week 144 for all patients, regardless of treatment arm or current treatment
  • All patients are to be encouraged to stay on the study up to week 144, to maximize follow up on study.
  Eligibility

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

Inclusion Criteria:

  • HIV-1 positive by licensed diagnostic test with presumed duration of infection > 6 months from date of randomisation.
  • Aged > 16 years of age (or minimum age as determined by local regulations or as legal requirements dictate).
  • Antiretroviral treatment naïve.
  • Qualifying plasma HIV RNA > 2,000 copies/mL and a CD4+ T cell count of ≥ 50 cells/µL.
  • No evidence of harbouring a drug resistant HIV (based upon genotypic drug testing).
  • Calculated creatinine clearance (CLCr) greater than or equal to 70 mL/min (Cockcroft-Gault formula).
  • Able to provide written informed consent.

Exclusion Criteria:

  • The following laboratory variables,

    • absolute neutrophil count (ANC) < 750 cells/µL
    • haemoglobin < 8.0 g/dL
    • platelet count < 50,000 cells/µL
    • serum AST, ALT > 5 x upper limit of normal (ULN)
    • serum bilirubin > 1.5 x ULN
  • Pregnant or nursing mothers.
  • Current use of human growth hormone, testosterone or other anabolic steroid.
  • Current use of any prohibited medications as described in product specific information.
  • Acute therapy for serious infection or other serious medical illness (in the judgement of the site Principal Investigator) requiring systemic treatment and/or hospitalisation.
  • Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial.
  • Patients unlikely to be able to remain in follow-up for the protocol-defined period.
  • Patients with known renal insufficiency.
  • Patients with obstructive liver disease.
  • Patients with intractable diarrhoea (six loose stools/day for at least seven consecutive days).
  • History of acute or chronic pancreatitis.
  • Presence of cardiomyopathy (due to any cause) or any significant cardiovascular disease, such as unstable ischemic heart disease.
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated).
  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: NCT00335322

Sponsors and Collaborators
Kirby Institute
The University of New South Wales
Investigators
Principal Investigator: David A Cooper, AO DSc MD FRACP FRCPA FRCP Kirby Institute
  More Information

Additional Information:
Publications:
Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT00335322     History of Changes
Other Study ID Numbers: NCHECR-ALTAIR
Study First Received: June 8, 2006
Results First Received: April 17, 2012
Last Updated: April 17, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Kirby Institute:
Human Immunodeficiency Virus (HIV)

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

ClinicalTrials.gov processed this record on September 15, 2014