Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects (HIV)
A prospective, randomized, open-label pilot study to assess virologic suppression and immunologic recovery associated with a two-drug antiretroviral regimen of Raltegravir and the protease inhibitor lopinavir/ritonavir (LPV/r) and a three drug regimen with Raltegravir and two nRTIs (emtricitabine/tenofovir) in HIV-1 infected treatment-naïve subjects.
Immunology Substudy added to determine the kinetics of recovery of CD4 T cells and subpopulations (regulatory T cell [T regs], TH-17 and TH1) after treatment initiation with Raltegravir based regimens and their relationship with functional CD8 T cells and if Raltegravir containing therapies leads to decreases in markers of gut microbial translocation and of cellular and soluble markers of immune activation.
|HIV Infections||Drug: Raltegravir & Lopinavir/ritonavir Drug: Raltegravir and emtricitabine/tenofovir||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Pilot Study to Assess Virologic Suppression and Immune Recovery With Raltegravir and Lopinavir/Ritonavir and Raltegravir and Emtricitabine/Tenofovir in HIV-1 Infected Treatment-naïve Subjects|
- Time to Confirmed Virologic Failure [ Time Frame: weeks ]time to confirmed viologic failure at 24 weeks (up to 48 weeks)
- Time to Virologic Failure [ Time Frame: week 24 (up to 48 weeks) ]time to virologic failure at week 24 (up to 48 weeks)
- Study Medication Toxicity-related Discontinuation . [ Time Frame: 48 weeks ]grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity
- Weeks to HIV-1 RNA <200 Copies/ml [ Time Frame: from date of treatment start to first week documented viral suppression ]time to viral suppression noted as week on study treatment to attain HIV-1 RNA < 200 copies/ml
- Change From Baseline CD4+ and CD8+ Cell Counts [ Time Frame: Baseline, Weeks 16 and 24 ]mean change in CD4+ and CD8+ T-lymphocytes counts from baseline (defined as the average of pre-entry and entry values) at weeks 16 and 24 in the two treatment arms
- Study Medication Tolerability [ Time Frame: date started study treatment to first week documented change study treatment up to week 48 ]study treatment tolerability as measured by number of subjects receiving study treatment who either discontinued or changed any component of study treatment
|Study Start Date:||April 2008|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Raltegravir & Lopinavir/ritonavir
Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
Drug: Raltegravir & Lopinavir/ritonavir
Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor
Active Comparator: Raltegravir & emtricitabine/tenofovir
Raltegravir 400 mg tablet bu mouth, every 12 hours for 48 weeks and tenofovir/embritcitabine 200 mg/100 mg table by mouth, once daily for 48 weeks
Drug: Raltegravir and emtricitabine/tenofovir
Three drug regimen of an integrase inhibitor and a fixed dose combination of a non-nucleoside/nucleotide inhibitors
A009 is a prospective, randomized, open-label pilot study to assess virologic suppression and immune recovery rates associated with a two-drug potent antiretroviral regimen of raltegravir and the protease inhibitor lopinavir/ritonavir and a three-drug regimen with raltegravir and two nRTIs (emtricitabine/tenofovir) in treatment-naïve subjects.
HIV-1-infected subjects who are antiretroviral drug-naïve and have plasma HIV-1 RNA levels ≥5000 copies/ml obtained within 30 days prior to study entry will be randomized 1:1 to Raltegravir 400 mg BID + LPV 400 mg/RTV 100 mg BID (Arm A) or Raltegravir 400 mg BID + FTC 200 mg/TDF 300 mg QD (Arm B).
Subjects will have measurements of HIV-1 RNA and CD4+ and CD8+ T-cell counts at pre-entry and entry. The average of these measurements will be used to establish their baseline values. Following entry, subjects will have plasma HIV-1 RNA samples drawn at days 2, 4, 8 and at weeks 2, 4, 8, 16, 24, 32, 40 and 48 and at virologic failure. CD38 expression on CD4+/CD8+ cells and CD38/HLA-DR activation antigen on CD4+ and CD8+ cells and subsets T-cell percentage will be done at entry, day 8 and weeks 4, 8, 24 and at virologic failure by advanced flow cytometry.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00654147
|United States, Florida|
|University of Miami AIDS Clinical Research Unit|
|Miami, Florida, United States, 33136|
|Study Chair:||Margaret A Fischl, M.D.||University of Miami AIDS Clinical Research Unit|