Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Kaletra + Isentress; Atripla
Intervention description: kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day; Atripla 1 tab once a day
Intervention MeSH terms: Ritonavir; Lopinavir; Tenofovir; Emtricitabine; Raltegravir Potassium; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV treatment; Treatment-naive; Adult

Summary:

      CCTG 589 is a randomized, open-label, pilot study comparing the efficacy, safety and
      tolerability of RAL plus LPV/r to EFV plus TDF/FTC in HIV-infected, treatment-naïve subjects.
      Subjects will be ineligible if they have any evidence of drug resistant virus in the past or
      at the time of screening (if never previously tested). Those who are found to be eligible
      will be randomized 1:1 to initiate either LPV/r (400/100 mg) plus RAL (400mg), both given
      twice-daily, or fixed dose combination of EFV (600 mg), TDF (300 mg) and FTC (200 mg) given
      as once-daily Atripla® for 48 weeks.

      Hypotheses

        1. The novel nucleoside-sparing combination of LPV/r + RAL will have a faster phase 1 viral
           decay rate compared to standard-of-care therapy with EFV/TDF/FTC in antiretroviral-naïve
           patients.

             1. Faster phase 1 viral decay dynamics will be associated with improved longer-term
                (week 48) viral suppression.

             2. Faster phase 1 viral decay dynamics will be associated with accelerated early (Day
                0-14) clearance of cell-associated HIV DNA.

             3. Faster phase 1 viral decay dynamics will be associated with greater early (baseline
                to week 12) CD4+ T-cell recovery.

        2. The LPV/r + RAL arm will have greater decreases in early (baseline to week 4) CD4/CD8
           T-cell immune activation and apoptosis which will be associated with greater late (week
           12 to week 48) CD4+ T-cell recovery.

        3. Subjects treated with LPV/r + RAL arm will have smaller changes in total cholesterol and
           triglycerides from baseline than those receiving EFV/TDF/FTC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented HIV-1 infection.

          -  Treatment naïve (defined as having never received any HIV antiretroviral agents in
             past).

          -  CD4+ T-cell count greater than or equal to 50 cells/mm3

          -  HIV viral load greater than or equal to 5,000 copies/mL

          -  Laboratory values obtained by screening laboratories within 30 days of entry:

               -  Absolute neutrophil count (ANC) greater than 750/mm3.

               -  Hemoglobin greater than 8.0 g/dL.

               -  Platelet count greater than 50,000/mm3.

               -  Calculated creatinine clearance (CrCl) > 60 mL/min as estimated by the
                  Cockcroft-Gault equation:

                    -  For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in
                       mg/dL x 72) = CrCl (mL/min)

                    -  For women, multiply the result by 0.85 = CrCl (mL/min)

               -  AST (SGOT), ALT (SGPT), and alkaline phosphatase less than 5 x ULN.

               -  Total bilirubin less than 2.5 x ULN.

          -  Females of childbearing potential must have a negative serum pregnancy test at
             screening and agree to use a double-barrier method of contraception throughout the
             study period.

          -  Men and women age greater than or equal to 18 years.

          -  Ability to obtain prescription for HIV antiretroviral medications and to have required
             prescriptions filled prior to entry.

          -  Ability and willingness of subject to give written informed consent

        Exclusion Criteria:

          -  Pregnancy or breast-feeding

          -  Serious illness requiring systemic treatment and/or hospitalization until subject
             either completes therapy or is clinically stable on therapy, in the opinion of the
             investigator, for at least 30 days prior to study entry (day 0).

          -  Acute therapy for serious infection or other serious medical illnesses (in the
             judgment of the site investigator) requiring systemic treatment and/or hospitalization
             within 14 days prior to study entry (day 0).

          -  Evidence of HIV seroconversion within 6 months prior to study entry.

          -  Evidence of any major HIV drug resistance-associated mutation on any genotype
             performed prior to study entry or at the time of screening.

          -  History of chronic hepatitis C (defined as HCV antibody positive and HCV RNA
             detectable).

          -  History of chronic active hepatitis B (defined as surface antigen positive and/or HBV
             DNA detectable).

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements.

          -  Use of any immunomodulator, HIV vaccine, or investigational therapy within 30 days of
             study entry.

          -  Use of human growth hormone within 30 days prior to study entry.

          -  Initiation of testosterone or anabolic steroids within 30 days prior to study entry.
             (Exception: Chronic replacement dosages in patient's with diagnosed hypogonadism is
             allowed).