Clinical trial NCT01154673: Effects of Intensive cART During Acute/Early HIV Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute HIV Infection
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
name: Maple Leaf Research
First posted: 2010-07-01
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

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

Primary outcomes:
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.
timeFrame: Baseline to Week 48
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic
state: Ontario
Study officials:
affiliation: University of Toronto
name: Mario Ostrowski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maple Leaf Research
name: Colin Kovacs, MD
role: PRINCIPAL_INVESTIGATOR
References: