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

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ClinicalTrials.gov Identifier: NCT00752856
Recruitment Status : Completed
First Posted : September 16, 2008
Results First Posted : July 7, 2020
Last Update Posted : July 22, 2020
Sponsor:
Collaborators:
California HIV/AIDS Research Program
Merck Sharp & Dohme Corp.
Abbott
Information provided by (Responsible Party):
Sheldon Morris, University of California, San Diego

Brief 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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Kaletra + Isentress Drug: Atripla Phase 2

Detailed Description:
The purpose of this study is to determine how well a new anti-HIV drug combination (RAL plus LPV/r) taken twice a day decreases the amount of HIV found in participants' blood (viral load) compared to taking the once-a-day combination pill Atripla®. This study will also try to determine if the new combination has fewer side effects and is tolerated better than Atripla®. Another reason this study is being done is to see if this new drug combination helps participants' body's CD4 cells recover differently and will also look at how well participants' bodies absorbs these drugs and how safe these drugs are when given together.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : August 26, 2008
Actual Primary Completion Date : May 5, 2011
Actual Study Completion Date : February 11, 2014


Arm Intervention/treatment
Experimental: 1 - Kaletra + Isentress taken twice daily
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 (LPV/r) + Raltegravir (RAL)

Active Comparator: 2 - Atripla taken once daily
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
Other Name: Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC)




Primary Outcome Measures :
  1. To Compare the Phase 1 Viral Decay Rates Between LPV/r + RAL vs. EFV/TDF/FTC Treatment Combinations. [ Time Frame: Baseline, days 2, 7, 10, 14 ]
    Repeated HIV RNA measured at different time points (baseline, days 2, 7, 10, 14) will be treated as the outcome variable in a linear mixed-effects model. The primary fixed effects will include time, treatment group, treatment group-by-time interaction; random effects will include both intercept and slope allowing each subject to have individual baseline viral load and viral decay (rate of decrease in viral load following initiation of antiretroviral therapy). The treatment group-by- time interaction term in the model will indicate the difference in viral decay rates between the two treatment groups. Baseline covariate adjustment will be included if necessary.


Secondary Outcome Measures :
  1. Viral Suppression Efficacy at 48 Weeks [ Time Frame: 48 weeks ]
    To determine the antiviral efficacy of LPV/r + RAL compared to EFV/TDF/FTC after 48 weeks of treatment by achieving undetectable viral load

  2. Compare Early Activated CD4+ T-cell Recovery Rates From Baseline to Week 4. [ Time Frame: Baseline to Week 4 ]
    To compare early (baseline to Week 4) activated CD4+ T-cell recovery rates between treatment regimens.

  3. Compare Late Activated CD4+ T-cell Recovery Rates Between Treatment Regimens From Baseline to Week 48 [ Time Frame: 48 weeks ]
    To compare late (baseline to Week 48) activated CD4+ T-cell recovery rates between treatment regimens.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00752856


Locations
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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
University of California, San Diego
California HIV/AIDS Research Program
Merck Sharp & Dohme Corp.
Abbott
Investigators
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Principal Investigator: Richard Haubrich, MD California Collaborative Treatment Group (CCTG)
Study Chair: Sheldon Morris, MD UC San Diego AntiViral Research Center (AVRC)
  Study Documents (Full-Text)

Documents provided by Sheldon Morris, University of California, San Diego:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sheldon Morris, Clinical Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00752856    
Other Study ID Numbers: CCTG 589
First Posted: September 16, 2008    Key Record Dates
Results First Posted: July 7, 2020
Last Update Posted: July 22, 2020
Last Verified: July 2020
Keywords provided by Sheldon Morris, University of California, San Diego:
HIV treatment
Treatment-naive
Adult
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Lopinavir
Tenofovir
Emtricitabine
Raltegravir Potassium
Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Efavirenz
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors