Effects of Intensive cART During Acute/Early HIV Infection

This study has been completed.
St. Michael's Hospital, Toronto
Maple Leaf Medical Clinic
Information provided by (Responsible Party):
Mario Ostrowski, University of Toronto
ClinicalTrials.gov Identifier:
First received: June 29, 2010
Last updated: March 4, 2016
Last verified: March 2016
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: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blinded, Controlled Trial of Intensive HAART Including Raltegravir, and Maraviroc, on HIV-1 Pro-viral DNA and Reservoir Decay in HIV-1-infected Individuals During the Acute/Early 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 ]
    The level of HIV Provirus in CD4 T cells obtained from peripheral blood at 48 weeks compared to baseline. A quantitative HIV PCR assay was done. The mean/median values from the standard HAART group is compared to the intensive HAART treatment regimen.

Enrollment: 32
Study Start Date: November 2011
Study Completion Date: September 2014
Primary Completion Date: September 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.

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

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
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: NCT01154673

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
Principal Investigator: Mario Ostrowski, MD University of Toronto
Principal Investigator: Colin Kovacs, MD Maple Leaf Medical Clinic
  More Information

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
Results First Received: October 26, 2015
Last Updated: March 4, 2016
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
CCR5 Receptor Antagonists
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
HIV Integrase Inhibitors
HIV Protease Inhibitors
Integrase Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2016