Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection
Condition: Infection, Human Immunodeficiency Virus I; HIV Infection
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Intervention: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r); Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV)
Intervention description: Abacavir (ABC)/lamivudine (3TC) FDC + atazanavir (ATV)+ ritoanvir (/r) for 36weeks followed by ABC/3TC + ATV + /r for 48wks followed by optional treatment extension for 60 weeks on the same regimen; Abacavir (ABC)/lamivudine (3TC) FDC + atazanavir (ATV) + ritonavir (/r) for 36 weeks followed by ABC/3TC + ATV for 48wks followed by optional treatment extension for 60 weeks on the same regimen
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate; Lamivudine; Abacavir; Dideoxynucleosides
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 515.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NORVIR; ARIES; EPZICOM; REYATAZ; HIV; simplification; Antiretroviral-naive

Summary:

      This study was designed to test the efficacy, safety, tolerability and durability of the
      antiviral response between atazanavir (ATV) + ritonavir (/r) + abacavir/lamivudine(ABC/3TC)
      Fixed dose combination (FDC) each administered once daily (QD) for 36 weeks followed by
      randomization to either a simplification regimen of ATV or continuation of ATV +/r for an
      additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1
      infected, HLA-B*5701 negative subjects.

      All subjects who complete the 84-week study will be eligible to enter the treatment extension
      phase and continue for an additional 60 weeks. The purpose of this extension is to obtain
      longer term treatment data in subjects who have completed the 84-week study.
    

Eligibility criteria:

        Inclusion criteria:

          -  Subject is ≥ 18 years of age and has documented evidence of HIV-1 infection. (A female
             is eligible to enter and participate in this study if she is of: non child-bearing
             potential, child bearing potential with a negative pregnancy test and agrees to
             approved contraception methods, or agreement for complete abstinence.)

          -  Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any
             NRTI and no prior therapy with either a PI or NNRTI).

          -  Subject has plasma HIV-1 RNA ≥ 1,000 copies/mL by Roche COBAS AMPLICOR™ (Version 1.5)
             method at screening (if no other documentation of HIV infection is available, a
             positive result here may serve as documentation of HIV infection for this study).

          -  Subject is willing and able to understand and provide written informed consent prior
             to participation in this study.

        Exclusion criteria:

          -  Subject is HLA-B*5701 positive.

          -  Subject testing positive for Hepatitis B or both Hepatitis B and Hepatitis C at
             screening (+ HbsAg)

          -  Genotyping results performed at the screening indicate that the subject has any of the
             following mutations at the reverse transcriptase (RT) enzyme: K65R, L74V, or Y115F, or
             a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E)
             that include changes at either L210 or T215, or ≥ 3 of the following protease
             mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50,
             I54, A71, G73, V77, V82, I84, N88, and L90.

          -  Women who are pregnant or breastfeeding.

          -  Subject has an active or acute CDC Clinical Category C event at screening. Treatment
             for the acute event must have been completed at least 30 days prior to screening.

          -  Subject is, in the opinion of the investigator, unable to complete the 84-week dosing
             period and protocol evaluations and assessments.

          -  Subject has ongoing clinically relevant pancreatitis or clinically relevant hepatitis
             at screening.

          -  Presence of a newly diagnosed HIV-related opportunistic infection or any medical
             condition requiring acute therapy at the time of enrollment.

          -  Subject suffers from a serious medical condition, such as diabetes, congestive heart
             failure, cardiomyopathy or other cardiac dysfunction (including known, clinically
             significant cardiac conduction system disease, severe first degree atrioventricular
             block [PR interval > 0.26 seconds], second or third-degree atrioventricular block),
             which in the opinion of the investigator would compromise the safety of the subject.

          -  Subject has pre-existing mental, physical, or substance abuse disorder, which in the
             opinion of the investigator would interfere with the subject's ability to comply with
             the dosing schedule and protocol evaluations and assessments.

          -  Subject has a history of inflammatory bowel disease or malignancy, intestinal
             ischemia, malabsorption, or other gastrointestinal dysfunction, which may interfere
             with drug absorption or render the subject unable to take oral medication.

          -  Subject requires treatment with foscarnet, hydroxyurea or other agents with documented
             activity against HIV-1 in vitro within 28 days of study administration.

          -  Subject requires treatment with immunomodulating agents (such as systemic
             corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to
             screening, or subject had received an HIV-1 immunotherapeutic vaccine within 90 days
             prior to screening. Subjects using inhaled corticosteroids are eligible for
             enrollment.

          -  Creatinine clearance <50 mL/min via the Cockroft-Gault method [Cockroft, 1976].

          -  Active alcohol or substance use sufficient, in the investigator's opinion, to prevent
             adequate compliance with study therapy or to increase the risk of developing
             pancreatitis or chemical hepatitis.

          -  Hypersensitivity to any component of the study drugs.

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper
             limit of normal (ULN).

          -  Total bilirubin > 1.5 times the upper limit of normal (ULN).

          -  Subject has any acute laboratory abnormality at screening, which, in the opinion of
             the investigator, would preclude the subject's participation in the study of an
             investigational compound. Any grade 4 laboratory abnormality would exclude a subject
             from study participation.

          -  Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents
             within 28 days prior to screening, or has an anticipated need for these agents within
             the study period.

          -  Enrolled in one or more investigational drug protocols, which may have impacted HIV-1
             RNA suppression.

          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious disease) illness must
             not be enrolled into this study.

          -  Subjects requiring concomitant administration of proton pump inhibitors.

          -  Subjects who require treatment with the prohibited medications within 28 days of
             commencement of investigational product, or an anticipated need during the study.

        Eligibility Criteria for Treatment Extension Phase:

        -Subjects will be eligible to continue in the treatment extension phase (Weeks 84 to 144)
        if they have successfully completed the 84-week study.