Fuzeon Viral Decay Pilot Study

A Pilot Randomized Controlled Trial of Adding Enfuvirtide to Standard Combination Antiretroviral Therapy in HIV-infected Individuals With Full Virologic Suppression to Further Suppress Proviral HIV DNA

In order to better understand the source(s) and the mechanism(s) of HIV persistence and to potentially lead to further suppression of HIV from viral reservoirs, we propose to examine the effect of co-administration of enfuvirtide, an entry inhibitor of HIV, on diminution of the size of the viral reservoir in infected individuals who are receiving effective antiviral therapy for extended periods of time (> 5 years).

Study Overview

• Status: Completed
• Conditions: HIV-1
• Intervention / Treatment: Drug: enfuvirtide

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1L6
      • Maple Leaf Medical Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient must be HIV infected
2. Patient must be > 18 years old
3. Patient must be taking standard combination antiretroviral therapy with 2-3 NRTIs and 1-2 PIs or a NNRTIs for at least five years
4. Patient must have a viral load < 50 copies/mL (using the standard available methods of detection) during the entire time on standard combination antiretroviral therapy except for initial fall of viral load
5. Patient must have a CD4 count above 400 cells/mm3 in last 3 months
6. Female patient must agree to use two methods of birth control or abstinence during the period of the study
7. Patient has to have signed full informed consent

Exclusion Criteria:

1. Patient who would have difficulty participating in a trial due to non-adherence or substance abuse
2. Patient who have taken mono or dual antiretroviral therapy
3. Patient who have had a viral load > 50 copies/mL on any antiretroviral regimen

4. Patient with any of the following abnormal laboratory test results in screening:

   • Hemaglobin < 100 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
5. Patient with a malignancy
6. Patient with other significant underlying disease (non-HIV) that might impinge upon disease progression or death
7. Patient with an active AIDS-defining illnesses in the past six months
8. Patients who are pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Did not receive enfuvirtide; patients were randomized to either receive enfuviratide or not receive it	Drug: enfuvirtide; 1ml BID
ACTIVE_COMPARATOR: enfuvirtide; enfuvirtide 1ml BID	Drug: enfuvirtide; 1ml BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of proviral HIV-1 DNA in both purified resting and activated CD4 T cells from baseline to month 6.	The change of proviral HIV-1 DNA in both purified resting and activated CD4 T cells from baseline to month 6.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the change of proviral HIV-1 DNA from baseline to month 3	To determine the change of proviral HIV-1 DNA from baseline to month 3	3 months
To determine the change of proviral HIV-1 DNA from months 6 to 9 after the enfurvitide has been stopped for 3 months in the treatment arm	To determine the change of proviral HIV-1 DNA from months 6 to 9 after the enfurvitide has been stopped for 3 months in the treatment arm	9 months
To quantify plasma HIV (limit of detection 2 copies/ml of plasma)	To quantify plasma HIV (limit of detection 2 copies/ml of plasma)	9 months
To quantify cell associated HIV RNA (unspliced and multiply spliced) in resting and activated CD4+ T cells	To quantify cell associated HIV RNA (unspliced and multiply spliced) in resting and activated CD4+ T cells	9 months
To determine the decay characteristics of HIV in resting CD4+ T cells by quantitative co-culture assays	To determine the decay characteristics of HIV in resting CD4+ T cells by quantitative co-culture assays	9 months
To determine the half-life of HIV in resting CD4+ T cells	To determine the half-life of HIV in resting CD4+ T cells	9months
To carry out phylogenetic analysis of HIV in the plasma, resting, and activated CD4+ T cell compartments	To carry out phylogenetic analysis of HIV in the plasma, resting, and activated CD4+ T cell	9 months
To quantify the amount of HIV in gastrointestinal-associated lymphoid tissue (GALT) by quantitative co-culture assays (as part of a sub-study - see GALT sub-study)	To quantify the amount of HIV in gastrointestinal-associated lymphoid tissue (GALT) by quantitative co-culture assays (as part of a sub-study - see GALT sub-study)	9 months

Collaborators and Investigators

• Sponsor: Canadian Immunodeficiency Research Collaborative
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Colin Kovacs, MD, University of Toronto

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (ACTUAL): July 1, 2007
• Study Completion (ACTUAL): January 1, 2010

Study Registration Dates

• First Submitted: June 2, 2006
• First Submitted That Met QC Criteria: June 2, 2006
• First Posted (ESTIMATE): June 6, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): June 5, 2012
• Last Update Submitted That Met QC Criteria: June 4, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Fuzeon; Viral Decay
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Enfuvirtide
• Other Study ID Numbers: Roche-FVD-1