Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00654147
- Lead Sponsor
- Margaret A. Fischl, M.D.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Raltegravir & emtricitabine/tenofovir Raltegravir and 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 Raltegravir & Lopinavir/ritonavir Raltegravir & Lopinavir/ritonavir Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
- Primary Outcome Measures
Name Time Method Time to Confirmed Virologic Failure weeks time to confirmed viologic failure at 24 weeks (up to 48 weeks)
Time to Virologic Failure week 24 (up to 48 weeks) time to virologic failure at week 24 (up to 48 weeks)
- Secondary Outcome Measures
Name Time Method Weeks to HIV-1 RNA <200 Copies/ml 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 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 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 Medication Toxicity-related Discontinuation . 48 weeks grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity
Trial Locations
- Locations (1)
University of Miami AIDS Clinical Research Unit
🇺🇸Miami, Florida, United States