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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Raltegravir & Lopinavir/ritonavir
Drug: Raltegravir and emtricitabine/tenofovir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 44
Study Start Date: April 2008
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Raltegravir & Lopinavir/ritonavir
Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
Drug: Raltegravir & Lopinavir/ritonavir
Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor
Other Names:
  • Isentress
  • Kaletra
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00654147

Locations
United States, Florida
University of Miami AIDS Clinical Research Unit
Miami, Florida, United States, 33136
Sponsors and Collaborators
Margaret A. Fischl, M.D.
Investigators
Study Chair: Margaret A Fischl, M.D. University of Miami AIDS Clinical Research Unit
  More Information

No publications provided

Responsible Party: Margaret A. Fischl, M.D., Professor of Medicine, Director AIDS Clinical Research Unit, University of Miami
ClinicalTrials.gov Identifier: NCT00654147     History of Changes
Other Study ID Numbers: A009
Study First Received: April 2, 2008
Results First Received: January 20, 2015
Last Updated: July 7, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
HIV
antiretroviral therapy naive
Integrase inhibitor
HIV/AIDS
treatment naïve

Additional relevant MeSH terms:
Emtricitabine
Integrase Inhibitors
Lopinavir
Ritonavir
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2015