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

June 29, 2010
May 27, 2013
November 2011
May 2014   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01154673 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 [ 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 ]
Not Provided
Not Provided
 
Intense Acute Infection Study
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

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Acute HIV Infection
  • 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
  • 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

    Interventions:
    • Drug: raltegravir
    • Drug: maraviroc
    • Drug: emtricitabine 200mg /tenofovir 300mg
    • Drug: lopinavir 400 mg/ritonavir 100mg
  • 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
    Interventions:
    • Drug: emtricitabine 200mg /tenofovir 300mg
    • Drug: lopinavir 400 mg/ritonavir 100mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
32
November 2016
May 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01154673
041009
Yes
Mario Ostrowski, University of Toronto
University of Toronto
  • St. Michael's Hospital, Toronto
  • Maple Leaf Medical Clinic
Principal Investigator: Mario Ostrowski, MD University of Toronto
Principal Investigator: Colin Kovacs, MD Maple Leaf Medical Clinic
University of Toronto
May 2013

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