Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients

This study has been completed.
Sponsor:
Collaborators:
California HIV/AIDS Research Program
Merck Sharp & Dohme Corp.
Abbott
Information provided by (Responsible Party):
California Collaborative Treatment Group
ClinicalTrials.gov Identifier:
NCT00752856
First received: September 13, 2008
Last updated: March 31, 2014
Last verified: March 2014

September 13, 2008
March 31, 2014
September 2008
November 2010   (final data collection date for primary outcome measure)
To compare the phase 1 viral decay rates between LPV/r + RAL vs. EFV/TDF/FTC treatment combinations. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00752856 on ClinicalTrials.gov Archive Site
  • To determine the antiviral efficacy of LPV/r + RAL compared to EFV/TDF/FTC after 48 weeks of treatment. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • To compare early (baseline to week 12) and late (week 12 to week 48) CD4+ T-cell recovery rates between treatment regimens. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • To evaluate the association of phase 1 viral decay dynamics (baseline to day 14) on phase 1 (baseline to week 12) CD4+ T-cell recovery. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • To evaluate the association of early changes in immune subsets (baseline to week 4) on phase 2 (week 12 to week 48) CD4+ T-cell recovery [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of this novel nucleoside-sparing combination of LPV/r + RAL compared to EFV/TDF/FTC therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients
Nucleoside-Sparing Combination Therapy With Lopinavir/Ritonavir (LPV/r) + Raltegravir (RAL) vs. Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC) in Antiretroviral-Naïve Patients

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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Kaletra + Isentress
    kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day
    Other Name: lopinavir ritonavir raltegravir
  • Drug: Atripla
    Atripla 1 tab once a day
  • Experimental: 1
    Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily
    Intervention: Drug: Kaletra + Isentress
  • Active Comparator: 2
    Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily
    Intervention: Drug: Atripla
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
November 2010
November 2010   (final data collection date for primary outcome measure)

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).
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00752856
CCTG 589
Yes
California Collaborative Treatment Group
California Collaborative Treatment Group
  • California HIV/AIDS Research Program
  • Merck Sharp & Dohme Corp.
  • Abbott
Not Provided
California Collaborative Treatment Group
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP