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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Raltegravir & Lopinavir/ritonavir; Drug: Raltegravir and emtricitabine/tenofovir

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami AIDS Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Confirmed Virologic Failure	time to confirmed viologic failure at 24 weeks (up to 48 weeks)	weeks
Time to Virologic Failure	time to virologic failure at week 24 (up to 48 weeks)	week 24 (up to 48 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Medication Toxicity-related Discontinuation .	grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity	48 weeks
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	from date of treatment start to first week documented viral suppression
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	Baseline, Weeks 16 and 24
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	date started study treatment to first week documented change study treatment up to week 48

Collaborators and Investigators

• Sponsor: Margaret A. Fischl, M.D.
• Investigators: Study Chair: Margaret A Fischl, M.D., University of Miami AIDS Clinical Research Unit

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: April 2, 2008
• First Submitted That Met QC Criteria: April 4, 2008
• First Posted (Estimate): April 7, 2008

Study Record Updates

• Last Update Posted (Estimate): August 3, 2015
• Last Update Submitted That Met QC Criteria: July 11, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: HIV; HIV/AIDS; treatment naïve; Integrase inhibitor; antiretroviral therapy naive
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Ritonavir; Lopinavir
• Other Study ID Numbers: A009