Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 2012

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.

Interventions

  • Drug: Raltegravir & Lopinavir/ritonavir
    • Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor
  • Drug: Raltegravir and emtricitabine/tenofovir
    • Three drug regimen of an integrase inhibitor and a fixed dose combination of a non-nucleoside/nucleotide inhibitors

Arms, Groups and Cohorts

  • Active Comparator: Raltegravir & Lopinavir/ritonavir
    • Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
  • 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

Clinical Trial Outcome Measures

Primary Measures

  • 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)

Secondary Measures

  • 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

Participating in This Clinical Trial

Inclusion Criteria

  • 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 Exclusion Criteria:

  • 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Margaret A. Fischl, M.D.
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Margaret A. Fischl, M.D., Professor of Medicine, Director AIDS Clinical Research Unit – University of Miami
  • Overall Official(s)
    • Margaret A Fischl, M.D., Study Chair, University of Miami AIDS Clinical Research Unit

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