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Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease

This study has been terminated.
(Study stopped 12/2010 due to poor enrollment. Only 15 of 60 needed enrolled.)
Sponsor:
Collaborators:
University of Chicago
University of Illinois at Chicago
Ruth M. Rothstein CORE Center
Abbott
Gilead Sciences
Information provided by (Responsible Party):
Allan Tenorio, MD, Rush University Medical Center
ClinicalTrials.gov Identifier:
NCT00775606
First received: October 17, 2008
Last updated: May 30, 2014
Last verified: May 2014

October 17, 2008
May 30, 2014
October 2008
December 2010   (final data collection date for primary outcome measure)
CD4+ (Cluster of Differentiation 4) T-cell Apoptosis [ Time Frame: 24 weeks from treatment initiation (baseline and week 24) ] [ Designated as safety issue: No ]
Change in the percentage of naive CD4 T-cells undergoing apoptosis as measured by propidium iodide staining. This is a lab test that measures the percentage of naive CD4 T-cells that are undergoing cell death. The change in this measure is obtained by determining the difference between the percentage of naive CD4 T-cells undergoing apoptosis at week 24 of treatment and the percentage undergoing apoptosis at baseline.
Rates of ex vivo CD4+ T-cell apoptosis [ Time Frame: 24 weeks after treatment initiation ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00775606 on ClinicalTrials.gov Archive Site
  • CD4+ T-cell Change [ Time Frame: 24 weeks after treatment initiation (baseline and week 24) ] [ Designated as safety issue: No ]
    This measures the change in CD4+ T-cells from baseline to week 24 of treatment.
  • Naive, Central Memory and Effector Memory CD4+ and CD8+ (Cluster of Differentiation 8) T-cell Frequency [ Time Frame: 4, 12 and 24 weeks after treatment initiation ] [ Designated as safety issue: No ]
  • Activated and Regulatory CD4+ and CD8+ T-cell Frequencies [ Time Frame: 4, 12 and 24 weeks after treatment initiation ] [ Designated as safety issue: No ]
  • Response to Immunization With Pneumococcus Polysaccharide and Tetanus-diphtheria Vaccines [ Time Frame: 4 weeks after treatment initiation ] [ Designated as safety issue: No ]
    Response to immunization with pneumococcus polysaccharide and tetanus-diphtheria vaccines was not done due to small sample size
  • CD4+ T-cell change [ Time Frame: 12, 24 and 48 weeks after treatment initiation ] [ Designated as safety issue: No ]
  • Naive, central memory and effector memory CD4+ and CD8+ T-cell frequency [ Time Frame: 4, 12 and 24 weeks after treatment initiation ] [ Designated as safety issue: No ]
  • activated and regulatory CD4+ and CD8+ T-cell frequencies [ Time Frame: 4, 12 and 24 weeks after treatment initiation ] [ Designated as safety issue: No ]
  • Response to immunization with pneumococcus polysaccharide and tetanus-diphtheria vaccines [ Time Frame: 4 weeks after treatment initiation ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease
A Phase 4 Study of the Effect on Immune Reconstitution of a Lopinavir/Ritonavir-Based Versus an Efavirenz-based HAART (Highly Active Antiretroviral Therapy) Regimen in Antiretroviral-Naïve Subjects With Advanced HIV Disease

The ideal anti-HIV medications for patients with advanced HIV disease is unknown. There is evidence that anti-HIV regimens that contain protease inhibitors can enhance immune function better than regimens that do not contain protease inhibitors. This is a study that will determine the difference in immune enhancement capabilities between an anti-HIV regimen that contains the protease inhibitor - lopinavir-ritonavir, and a regimen that contains efavirenz. Both medications are recommended as first line treatments for HIV-infected patients. This study will recruit HIV-positive patients that need to start anti-HIV treatment because their CD4+ T-cells are below 200. The usual threshold for starting treatment is a CD4+ T-cell less than 350. Subjects will be randomized to treatment with either an anti-HIV regimen that contains lopinavir-ritonavir or a regimen that contains efavirenz. The study will determine the difference in immune reconstitution over 24 weeks of treatment with study medications. Among the immune parameters that will be measured is the ability of each subject to respond to vaccination with the tetanus-diphtheria vaccine and the 23-valent pneumococcal vaccine. Both vaccines are also recommended for HIV-positive patients but HIV-positive patients tend to have a lower response rate to these vaccines.

DESIGN: ICE-001 is a phase IV, randomized, two-arm unblinded study, comparing the effect on immune reconstitution of open-label ritonavir (RTV)-enhanced lopinavir (LPV) to efavirenz (EFV), in combination with daily emtricitabine (FTC)/tenofovir (TDF) as initial therapy for HIV-1 infection in HIV-infected treatment naïve subjects with CD4+ T-cells less than 200 cells/ml.

DURATION: Subjects will participate in ICE-001 for approximately 48 weeks after starting study treatment.

SAMPLE SIZE: ICE-001 will enroll 60 subjects (30 per treatment arm).

POPULATION: HIV-1-infected, antiretroviral (ARV) drug-naïve (≤7 days of ARV treatment at anytime prior to study entry) men and women between18 to 60 years of age with plasma HIV-1 RNA levels >1000 copies/mL and CD4+ T-cell counts < 200 cells/ml obtained within 90 days prior to study entry.

STRATIFICATION: Subjects will be stratified at screening based on plasma HIV-1 RNA levels <100,000 and ≥100,000 copies/mL.

REGIMEN: At entry subjects will be randomized to one of the following:

  • ARM A: LPV 400 mg/RTV 100 mg BID + FTC 200 mg/TDF 300 mg QD
  • ARM B: EFV 600 mg QD/FTC 200 mg/TDF 300 mg fixed dose combination QD

The objective is to determine the differences in the degree of immune reconstitution in HIV-infected patients with a CD4+ T-cell count < 200 cells/ml who initiated treatment with LPV/RTV + FTC/TDF compared to EFV/FTC/TDF.

Study visits will occur at screening, pre-entry, entry and weeks 1, 4, 8, 12, 24 and 48 after study entry. Study medications will be provided at entry after randomization. At most study visits, clinical assessments, including histories, physical exams and determination of drug adherence, will occur. Blood for hematologic and metabolic safety assessments and for the assessment of immune parameters will be obtained. Immune parameters that will be measured include levels of T-cell apoptosis, maturation and activation. Frequencies of various T-cell subsets and other lymphocyte populations will also be done. Response to vaccination with tetanus-diphtheria vaccine and 23-valent pneumococcal polysaccharide vaccine (both given at week 8) will be measured.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Acquired Immune Deficiency Syndrome
  • Drug: Lopinavir 400 mg/ritonavir 100 mg
    Lopinavir 400 mg/ritonavir 100 mg fixed dose combination BID + emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
    Other Names:
    • Kaletra
    • Truvada
  • Drug: Efavirenz
    Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
    Other Name: Atripla
  • Active Comparator: ARM A/Lopinar/ritonavir
    Subjects randomized to Arm A initiated Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD
    Intervention: Drug: Lopinavir 400 mg/ritonavir 100 mg
  • Active Comparator: ARM B/Efavirenz
    Subjects randomized to Arm B initiated Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
    Intervention: Drug: Efavirenz
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
15
January 2011
December 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. HIV-1 infection
  2. The absence of exclusionary resistance mutations on a genotypic resistance assay
  3. Antiretroviral (ARV) drug-naïve
  4. Screening HIV-1 RNA >1000 copies/mL
  5. Screening CD4+ T-cell count < 200 cells/ml
  6. Laboratory values obtained within 30 days prior to study entry.

    • Absolute neutrophil count (ANC) >500/mm3
    • Hemoglobin >8.0 g/dL
    • Platelet count >40,000/mm3
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 x ULN
    • Total bilirubin <2.5 x ULN
    • Calculated creatinine clearance ≥60 mL/min (by Cockcroft-Gault equation)
  7. For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications.
  8. Contraception requirements
  9. Men and women age >18 years and < 60 years.
  10. Ability and willingness of subject or legal guardian/representative to give written informed consent.

Exclusion Criteria:

  1. Currently breast-feeding.
  2. Use of immunomodulators, vaccines, growth hormone, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
  3. Known allergy/sensitivity to study drugs, pneumococcal polysaccharide vaccine, tetanus-diphtheria vaccine
  4. Receipt of pneumococcal polysaccharide vaccine or tetanus-diphtheria vaccine in the past 5 years.
  5. Active drug or alcohol use or dependence
  6. Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 14 days prior to study entry.
  7. Requirement for any current medications that are prohibited with any study treatment.
  8. Evidence of any major resistance-associated mutation on any genotype or evidence of significant resistance on any phenotype performed at any time prior to study entry
  9. Current or anticipated imprisonment or involuntary incarceration in a medical facility for psychiatric or physical (e.g., infectious disease) illness
  10. History of, or current bipolar disorder, major depression, schizophrenia or other psychotic disorders
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00775606
ICE-001
No
Allan Tenorio, MD, Rush University Medical Center
Rush University Medical Center
  • University of Chicago
  • University of Illinois at Chicago
  • Ruth M. Rothstein CORE Center
  • Abbott
  • Gilead Sciences
Study Chair: Allan R. Tenorio, M.D. Rush University Medical Center
Rush University Medical Center
May 2014

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