Intense Acute Infection Study
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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/tenofovir Drug: lopinavir/ritonavir |
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 |
- 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 ]
- 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 ]
| Estimated Enrollment: | 32 |
| Study Start Date: | September 2010 |
| Estimated Study Completion Date: | September 2016 |
| Estimated Primary Completion Date: | September 2012 (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:
Drug: maraviroc
Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART
Other Names:
Drug: emtricitabine/tenofovir
emtricitabine 200mg /tenofovir 300mg QD
Other Name: Truvada
Drug: lopinavir/ritonavir
lopinavir 400 mg/ritonavir 100mg BID
Other Names:
|
|
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/tenofovir
emtricitabine 200mg /tenofovir 300mg QD
Other Name: Truvada
Drug: lopinavir/ritonavir
lopinavir 400 mg/ritonavir 100mg BID
Other Names:
|
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 |
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:
- Positive HIV-1 antibody test result (Western blot), with a documented negative test result in the previous six months or
- 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
- 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:
- Participants who would have difficulty participating in a trial due to non-adherence or substance abuse
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
- Participant with a malignancy
- Participant with other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death
- Participant who is pregnant or who is trying to conceive
Contacts and Locations| Contact: Erika Benko, RN | 416-465-0856 ext 290 | erika@mapleleafmedical.com |
| Canada, Ontario | |
| University of Toronto | Not yet recruiting |
| Toronto, Ontario, Canada, M5B 1W8 | |
| Principal Investigator: Mario Ostrowski, MD | |
| Sub-Investigator: Rupert Kaul, MD, PhD | |
| Maple Leaf Medical Clinic | Not yet recruiting |
| Toronto, Ontario, Canada, M5B 1L6 | |
| Principal Investigator: Colin Kovacs, MD | |
| Sub-Investigator: Mona Loutfy, MD | |
| 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, 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: | June 29, 2010 |
| Health Authority: | Canada: Health Canada Therapeutic Products Directorate |
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 May 23, 2013