Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease
|Acquired Immune Deficiency Syndrome||Drug: Lopinavir 400 mg/ritonavir 100 mg Drug: Efavirenz||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||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|
- CD4+ (Cluster of Differentiation 4) T-cell Apoptosis [ Time Frame: 24 weeks from treatment initiation (baseline and week 24) ]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.
- CD4+ T-cell Change [ Time Frame: 24 weeks after treatment initiation (baseline and week 24) ]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 ]
- Activated and Regulatory CD4+ and CD8+ T-cell Frequencies [ Time Frame: 4, 12 and 24 weeks after treatment initiation ]
- Response to Immunization With Pneumococcus Polysaccharide and Tetanus-diphtheria Vaccines [ Time Frame: 4 weeks after treatment initiation ]Response to immunization with pneumococcus polysaccharide and tetanus-diphtheria vaccines was not done due to small sample size
|Study Start Date:||October 2008|
|Study Completion Date:||January 2011|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
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
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
Active Comparator: ARM B/Efavirenz
Subjects randomized to Arm B initiated Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
Other Name: Atripla
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00775606
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|University of Illinois Medical Center|
|Chicago, Illinois, United States, 60612|
|Howard Brown Health Center|
|Chicago, Illinois, United States, 60613|
|University of Chicago Hospital|
|Chicago, Illinois, United States, 60637|
|Study Chair:||Allan R. Tenorio, M.D.||Rush University Medical Center|