A prospective, randomized, open-label pilot study to assess virologic suppression and
immunologic recovery rates associated with a Two-drug antiretroviral regimen of Raltegravir
and the protease inhibitor lopinavir/ritonavir (LPV/r) and 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
RAL in the two treatment arms and their relationship with functional CD8 T cells and if RAL
containing therapies lead to a decrease 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.
- Documented HIV Infection
- Genotypic resistance without major resistance mutations within 30 days
- Antiretroviral drug-naïve
- Screening HIV-1 RNA ≥5000
- Women of reproductive potential
- Negative pregnancy test within 48 hours
- Acute or recent HIV-1 infection
- Currently breast feeding
- Use of immunomodulators
- Evidence of major resistance mutations
- HBsAg positive
- Acute hepatitis of any etiology or clinically significant liver disease
- Current imprisonment or involuntary incarceration