Effects of Intensive cART During Acute/Early HIV Infection

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Acute HIV Infection

Intervention / Treatment
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* Drug: raltegravir
* Drug: maraviroc
* Drug: emtricitabine 200mg /tenofovir 300mg
* Drug: lopinavir 400 mg/ritonavir 100mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive HAART<br>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<br>* Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART<br>* Other names: MK-0518;Drug: maraviroc<br>* Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART<br>* Other names: Selzentry;Drug: emtricitabine 200mg /tenofovir 300mg<br>* emtricitabine 200mg /tenofovir 300mg QD<br>* Other names: Truvada;Drug: lopinavir 400 mg/ritonavir 100mg<br>* lopinavir 400 mg/ritonavir 100mg BID<br>* Other names: Aluvia;|
| Placebo Comparator: Placebo Arm<br>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<br>* emtricitabine 200mg /tenofovir 300mg QD<br>* Other names: Truvada;Drug: lopinavir 400 mg/ritonavir 100mg<br>* lopinavir 400 mg/ritonavir 100mg BID<br>* Other names: Aluvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Baseline to Week 48 |