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
  Purpose

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.

Condition Intervention Phase
HIV Infections
Drug: Kaletra + Isentress
Drug: Atripla
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nucleoside-Sparing Combination Therapy With Lopinavir/Ritonavir (LPV/r) + Raltegravir (RAL) vs. Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC) in Antiretroviral-Naïve Patients

Resource links provided by NLM:


Further study details as provided by California Collaborative Treatment Group:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 50
Study Start Date: September 2008
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily
Drug: Kaletra + Isentress
kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day
Other Name: lopinavir ritonavir raltegravir
Active Comparator: 2
Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily
Drug: Atripla
Atripla 1 tab once a day

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  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: NCT00752856

Locations
United States, California
Living Hope Clinical Foundation
Long Beach, California, United States, 90813
University Southern California
Los Angeles, California, United States, 90033
Univerisity California Irvine
Orange, California, United States, 92868
Desert AIDS Project
Palm Springs, California, United States, 92262
University California San Diego
San Diego, California, United States, 92103
Harbor-UCLA
Torrance, California, United States, 90502
Sponsors and Collaborators
California Collaborative Treatment Group
California HIV/AIDS Research Program
Merck Sharp & Dohme Corp.
Abbott
  More Information

No publications provided

Responsible Party: California Collaborative Treatment Group
ClinicalTrials.gov Identifier: NCT00752856     History of Changes
Other Study ID Numbers: CCTG 589
Study First Received: September 13, 2008
Last Updated: March 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by California Collaborative Treatment Group:
HIV treatment
Treatment-naive
Adult

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
Ritonavir
Lopinavir
Tenofovir
Tenofovir disoproxil
Efavirenz
Emtricitabine
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014