Intense Acute Infection Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
St. Michael's Hospital, Toronto
Maple Leaf Medical Clinic
Information provided by (Responsible Party):
Mario Ostrowski, University of Toronto
ClinicalTrials.gov Identifier:
NCT01154673
First received: June 29, 2010
Last updated: May 27, 2013
Last verified: May 2013
  Purpose

This trial will investigate the efficacy and safety of intensified antiretroviral treatment that includes raltegravir and maraviroc during the early stages of HIV infection. With the proven efficacy of these antiviral drugs in pre- and post-clinical trials, we would like to investigate the ability of the combination of raltegravir and maraviroc plus a standard HAART backbone to further decrease the viral load in acutely infected treated HIV infected individuals.


Condition Intervention Phase
Acute HIV Infection
Drug: raltegravir
Drug: maraviroc
Drug: emtricitabine 200mg /tenofovir 300mg
Drug: lopinavir 400 mg/ritonavir 100mg
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blinded, Controlled Trial Assessing the Effect of Intensive Treatment With HAART and the Integrase Inhibitor, Raltegravir, and the CCR5 -Receptor Antagonist, Maraviroc, on HIV-1 Pro-viral DNA and Reservoir Decay in HIV-1-infected Individuals Initiating Antiretroviral Therapy During the Acute Phase of Infection

Resource links provided by NLM:


Further study details as provided by University of Toronto:

Primary Outcome Measures:
  • Change in proviral HIV-1 DNA in total CD4+ T-cells from baseline to week 48 in participants randomized to the intensified arm versus the control arm who received placebo in addition to standard HAART. [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determination of first phase HIV-1 viral decay: For comparison of plasma viral decay slopes, HIV-1 RNA collected during the first 8 weeks of the study will be used. [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Change in GALT HIV-1 proviral DNA from baseline to week 48: The mean values will be compared from baseline to week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change in plasma viremia to week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change of cell-associated HIV-1 RNA in CD4+ T cells to 48 weeks [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change of replication-competent HIV-1 in CD4+ T cells in blood to 48 week [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Determination of the half-life of HIV-1 proviral DNA in blood and GALT [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change in HIV-1 DNA and RNA levels in semen to 48 weeks [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • HIV-1 specific CD4+ and CD8+ T cell immune responses to week 48 in peripheral blood and GALT [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Peripheral CD4 count response to week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • CD4+ levels in GALT at week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: November 2011
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intensive HAART

Patients in this arm will receive the following HAART regimen:

Raltegravir 400 mg BID + Maraviroc 150mg BID + emtricitabine 200mg /tenofovir 300mg QD + lopinavir 400 mg/ritonavir 100mg BID for 96 weeks

Drug: raltegravir
Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART
Other Names:
  • Isentress
  • MK-0518
Drug: maraviroc
Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART
Other Names:
  • Celsentri
  • Selzentry
Drug: emtricitabine 200mg /tenofovir 300mg
emtricitabine 200mg /tenofovir 300mg QD
Other Name: Truvada
Drug: lopinavir 400 mg/ritonavir 100mg
lopinavir 400 mg/ritonavir 100mg BID
Other Names:
  • Kaletra
  • Aluvia
Placebo Comparator: Placebo Arm
Placebo (in place of raltegravir and maraviroc) will be added to standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400 mg/ritonavir 100mg BID) for 48 weeks and then offered open label Raltegravir and Maraviroc after 48 weeks
Drug: emtricitabine 200mg /tenofovir 300mg
emtricitabine 200mg /tenofovir 300mg QD
Other Name: Truvada
Drug: lopinavir 400 mg/ritonavir 100mg
lopinavir 400 mg/ritonavir 100mg BID
Other Names:
  • Kaletra
  • Aluvia

Detailed Description:

The trial is a prospective, randomized, double-blinded, placebo-controlled study with follow-up to 5 years. Thirty-two individuals presenting with newly diagnosed acute or early HIV-1 infection as described in the inclusion criteria will be enrolled, with sixteen randomized to each arm. Individuals will be randomized to one of two arms: the "Intensive" arm with standard HAART (Emtricitabine 200mg /tenofovir 300mg QD + Lopinavir 400mg /ritonavir 100mg BID) + Raltegravir + Maraviroc or the "placebo" arm with standard HAART+ Placebo for 48 weeks. Another group of individuals diagnosed with acute or early HIV-1 who elect to forego early treatment will be followed as non-randomized, untreated controls. At week 48, all patients will be informed of study results. If results are positive in the intensive treatment group, the placebo group will be offered to roll-over to the intense treatment arm and followed as an open-label cohort out to five years. Participants may stop treatment at any time and withdraw from the study. If they choose to do so, they will be followed according to the standards employed for all HIV-1 patients at the Maple Leaf clinic. At the five year point, the decision to terminate treatment will be made based on the existing state of the HIV-1 literature at the time.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

The major single criterion for inclusion into the study will be the presence of confirmed acute/early HIV-1 infection, as defined by one of the three following criteria:

  1. Positive HIV-1 antibody test result (Western blot), with a documented negative test result in the previous six months or
  2. Positive or weakly positive HIV-1 antibody screening ELISA test result, with indeterminate and evolving confirmatory test result with demonstrated HIV-1 antigenemia (p24 antigen test result) or viremia (HIV-1 bDNA ≥ 500 copies/ml) or
  3. Negative HIV-1 antibody test result in the setting of an illness compatible with acute seroconversion with demonstrated HIV-1 antigenemia (p24 antigen test result) or plasma viremia (HIV-1 bDNA ≥ 500 copies/ml)

Other inclusion criteria are:

  • Ages 18 or older
  • Ability to provide informed consent
  • HIV-1 viral load ≥ 5,000 copies/ml

Exclusion Criteria:

  1. Participants who would have difficulty participating in a trial due to non-adherence or substance abuse
  2. Participants with any of the following abnormal laboratory test results in screening:

    • Hemoglobin < 85 g/L
    • Neutrophil count < 750 cells/uL
    • Platelet count < 50,000 cells/L
    • AST or ALT > 5X the upper limit of normal
    • Creatinine > 250 umol/L
  3. Participant with a malignancy
  4. Participant with other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death
  5. Participant who is pregnant or who is trying to conceive
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01154673

Locations
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5B 1W8
Maple Leaf Medical Clinic
Toronto, Ontario, Canada, M5G 1K2
Sponsors and Collaborators
University of Toronto
St. Michael's Hospital, Toronto
Maple Leaf Medical Clinic
Investigators
Principal Investigator: Mario Ostrowski, MD University of Toronto
Principal Investigator: Colin Kovacs, MD Maple Leaf Medical Clinic
  More Information

No publications provided

Responsible Party: Mario Ostrowski, Principal Investigator, University of Toronto
ClinicalTrials.gov Identifier: NCT01154673     History of Changes
Obsolete Identifiers: NCT01101516
Other Study ID Numbers: 041009
Study First Received: June 29, 2010
Last Updated: May 27, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Lopinavir
Tenofovir
Tenofovir disoproxil
Emtricitabine
Integrase Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014