Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects (HIV)
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Raltegravir & Lopinavir/ritonavir
Raltegravir and emtricitabine/tenofovir
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring HIV, antiretroviral therapy naive, Integrase inhibitor, HIV/AIDS, treatment naïve
Eligibility 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
Sites / Locations
- University of Miami AIDS Clinical Research Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Raltegravir & Lopinavir/ritonavir
Raltegravir & emtricitabine/tenofovir
Arm Description
Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
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
Outcomes
Primary Outcome Measures
Time to Confirmed Virologic Failure
time to confirmed viologic failure at 24 weeks (up to 48 weeks)
Time to Virologic Failure
time to virologic failure at week 24 (up to 48 weeks)
Secondary Outcome Measures
Study Medication Toxicity-related Discontinuation .
grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity
Weeks to HIV-1 RNA <200 Copies/ml
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
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
study treatment tolerability as measured by number of subjects receiving study treatment who either discontinued or changed any component of study treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00654147
Brief Title
Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects
Acronym
HIV
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Margaret A. Fischl, M.D.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV, antiretroviral therapy naive, Integrase inhibitor, HIV/AIDS, treatment naïve
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Raltegravir & Lopinavir/ritonavir
Arm Type
Active Comparator
Arm Description
Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
Arm Title
Raltegravir & emtricitabine/tenofovir
Arm Type
Active Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Raltegravir & Lopinavir/ritonavir
Other Intervention Name(s)
Isentress, Kaletra
Intervention Description
Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor
Intervention Type
Drug
Intervention Name(s)
Raltegravir and emtricitabine/tenofovir
Other Intervention Name(s)
Isentress, Truvada
Intervention Description
Three drug regimen of an integrase inhibitor and a fixed dose combination of a non-nucleoside/nucleotide inhibitors
Primary Outcome Measure Information:
Title
Time to Confirmed Virologic Failure
Description
time to confirmed viologic failure at 24 weeks (up to 48 weeks)
Time Frame
weeks
Title
Time to Virologic Failure
Description
time to virologic failure at week 24 (up to 48 weeks)
Time Frame
week 24 (up to 48 weeks)
Secondary Outcome Measure Information:
Title
Study Medication Toxicity-related Discontinuation .
Description
grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity
Time Frame
48 weeks
Title
Weeks to HIV-1 RNA <200 Copies/ml
Description
time to viral suppression noted as week on study treatment to attain HIV-1 RNA < 200 copies/ml
Time Frame
from date of treatment start to first week documented viral suppression
Title
Change From Baseline CD4+ and CD8+ Cell Counts
Description
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
Time Frame
Baseline, Weeks 16 and 24
Title
Study Medication Tolerability
Description
study treatment tolerability as measured by number of subjects receiving study treatment who either discontinued or changed any component of study treatment
Time Frame
date started study treatment to first week documented change study treatment up to week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret A Fischl, M.D.
Organizational Affiliation
University of Miami AIDS Clinical Research Unit
Official's Role
Study Chair
Facility Information:
Facility Name
University of Miami AIDS Clinical Research Unit
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects
We'll reach out to this number within 24 hrs