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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Margaret A. Fischl, M.D., University of Miami
ClinicalTrials.gov Identifier:
NCT00654147
First received: April 2, 2008
Last updated: July 7, 2015
Last verified: July 2015

April 2, 2008
July 7, 2015
April 2008
January 2012   (final data collection date for primary outcome measure)
  • Time to Confirmed Virologic Failure [ Time Frame: weeks ] [ Designated as safety issue: No ]
    weeks to first plasma HIV-RNA level ≥1000 copies/ml
  • Time to Virologic Failure [ Time Frame: week 24 (up to 48 weeks) ] [ Designated as safety issue: No ]
    time to first plasma HIV-RNA level ≥1000 copies/ml
  • time to confirmed virologic failure (plasma HIV-1 RNA levels ≥1000 copies/ml [ Time Frame: at or after week 16 and before week 24, or ≥200 copies/ml at or after week 24) ] [ Designated as safety issue: No ]
  • study medication toxicity-related discontinuation of any component of the initial randomized study regimen. [ Time Frame: anytime during treatment ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00654147 on ClinicalTrials.gov Archive Site
  • Study Medication Toxicity-related Discontinuation . [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    study treatment tolerability as measured by number of subjects receiving study treatment who either discontinued or changed any component of study treatment
  • to compare virologic responses (confirmed plasma HIV-1 RNA <200 copies/ml and <50 copies/ml) in the two treatment arms. [ Time Frame: weeks 4, 8, 16, 24, 32, 40 and 48 ] [ Designated as safety issue: No ]
  • evaluate immunologic response defined as increases in CD4+ and CD8+ cell counts in the two treatment arms [ Time Frame: weeks 4, 8, 16, 24, 32, 40 and 48 ] [ Designated as safety issue: No ]
  • determine the safety and tolerability (proportion of subjects receiving study treatment) in the two treatment arms [ Time Frame: weeks 4, 8, 16, 24, 32, 40 and 48 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects
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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Raltegravir & Lopinavir/ritonavir
    Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor
    Other Names:
    • Isentress
    • Kaletra
  • Drug: Raltegravir and emtricitabine/tenofovir
    Three drug regimen of an integrase inhibitor and a fixed dose combination of a non-nucleoside/nucleotide inhibitors
    Other Names:
    • Isentress
    • Truvada
  • Active Comparator: Raltegravir & Lopinavir/ritonavir
    Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
    Intervention: Drug: Raltegravir & Lopinavir/ritonavir
  • 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
    Intervention: Drug: Raltegravir and emtricitabine/tenofovir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
44
January 2012
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00654147
A009
Yes
Margaret A. Fischl, M.D., University of Miami
Margaret A. Fischl, M.D.
Not Provided
Study Chair: Margaret A Fischl, M.D. University of Miami AIDS Clinical Research Unit
University of Miami
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP