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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor
Three drug regimen of an integrase inhibitor and a fixed dose combination of a non-nucleoside/nucleotide inhibitors
University of Miami AIDS Clinical Research Unit
Miami, Florida, United States
Time to Confirmed Virologic Failure
time to confirmed viologic failure at 24 weeks (up to 48 weeks)
Time frame: weeks
Time to Virologic Failure
time to virologic failure at week 24 (up to 48 weeks)
Time frame: week 24 (up to 48 weeks)
Study Medication Toxicity-related Discontinuation .
grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity
Time frame: 48 weeks
Weeks to HIV-1 RNA <200 Copies/ml
time to viral suppression noted as week on study treatment to attain HIV-1 RNA \< 200 copies/ml
Time frame: from date of treatment start to first week documented viral suppression
Change From Baseline CD4+ and CD8+ Cell Counts
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
Time frame: Baseline, Weeks 16 and 24
Study Medication Tolerability
study treatment tolerability as measured by number of subjects receiving study treatment who either discontinued or changed any component of study treatment
Time frame: date started study treatment to first week documented change study treatment up to week 48
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