Effects of Intensive cART During Acute/Early HIV Infection

NCT ID: NCT01154673

Last Updated: 2016-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-09-30

Brief Summary

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

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.

Conditions

Acute HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

raltegravir

Intervention Type: DRUG

Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART

maraviroc

Intervention Type: DRUG

Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART

emtricitabine 200mg /tenofovir 300mg

Intervention Type: DRUG

emtricitabine 200mg /tenofovir 300mg QD

lopinavir 400 mg/ritonavir 100mg

Intervention Type: DRUG

lopinavir 400 mg/ritonavir 100mg BID

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

Group Type: PLACEBO_COMPARATOR

emtricitabine 200mg /tenofovir 300mg

Intervention Type: DRUG

emtricitabine 200mg /tenofovir 300mg QD

lopinavir 400 mg/ritonavir 100mg

Intervention Type: DRUG

lopinavir 400 mg/ritonavir 100mg BID

Interventions

raltegravir

Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART

Intervention Type: DRUG

maraviroc

Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART

Intervention Type: DRUG

emtricitabine 200mg /tenofovir 300mg

emtricitabine 200mg /tenofovir 300mg QD

Intervention Type: DRUG

lopinavir 400 mg/ritonavir 100mg

lopinavir 400 mg/ritonavir 100mg BID

Intervention Type: DRUG

Other Intervention Names

Isentress; MK-0518; Celsentri; Selzentry; Truvada; Kaletra; Aluvia

Eligibility 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)

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Unity Health Toronto

OTHER

Sponsor Role: collaborator

Maple Leaf Research

OTHER

Sponsor Role: collaborator

University of Toronto

OTHER

Sponsor Role: lead

Responsible Party

Mario Ostrowski

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mario Ostrowski, MD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Colin Kovacs, MD

Role: PRINCIPAL_INVESTIGATOR

Maple Leaf Research

Locations

University of Toronto

Toronto, Ontario, Canada

Maple Leaf Medical Clinic

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

041009

Identifier Type: -

Identifier Source: org_study_id

NCT01101516

Identifier Type: -

Identifier Source: nct_alias