Intense Acute Infection Study

Acute HIV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01154673
• Other study ID #: 041009
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: June 29, 2010
• Last updated: May 29, 2015
• Start date: November 2011
• Est. completion date: September 2014

Study information

• Verified date: May 2015
• Source: University of Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01101516

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute HIV Infection
• Infection

Intervention

Drug:
• raltegravir
Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART
• maraviroc
Raltegravir 400 mg BID + Maraviroc 150mg BID in addition to standard HAART
• emtricitabine 200mg /tenofovir 300mg
emtricitabine 200mg /tenofovir 300mg QD
• lopinavir 400 mg/ritonavir 100mg
lopinavir 400 mg/ritonavir 100mg BID

Locations

Country	Name	City	State
Canada	Maple Leaf Medical Clinic	Toronto	Ontario
Canada	University of Toronto	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
University of Toronto	Maple Leaf Medical Clinic, St. Michael's Hospital, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Baseline to Week 48	No
Secondary	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.		Baseline to Week 8	No
Secondary	Change in GALT HIV-1 proviral DNA from baseline to week 48: The mean values will be compared from baseline to week 48		Baseline to Week 48	No
Secondary	Change in plasma viremia to week 48		Baseline to Week 48	No
Secondary	Change of cell-associated HIV-1 RNA in CD4+ T cells to 48 weeks		Baseline to Week 48	No
Secondary	Change of replication-competent HIV-1 in CD4+ T cells in blood to 48 week		Baseline to Week 48	No
Secondary	Determination of the half-life of HIV-1 proviral DNA in blood and GALT		Baseline to Week 48	No
Secondary	Change in HIV-1 DNA and RNA levels in semen to 48 weeks		Baseline to Week 48	No
Secondary	HIV-1 specific CD4+ and CD8+ T cell immune responses to week 48 in peripheral blood and GALT		Baseline to Week 48	No
Secondary	Peripheral CD4 count response to week 48		Baseline to Week 48	No
Secondary	CD4+ levels in GALT at week 48		Baseline to Week 48	No