Clinical trial NCT00334022: Fuzeon Viral Decay Pilot Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1
Keywords: Fuzeon
Viral Decay
Lead sponsor: Canadian Immunodeficiency Research Collaborative
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2006-06-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: The change of proviral HIV-1 DNA in both purified resting and activated CD4 T cells from baseline to month 6.
timeFrame: 6 months
Secondary outcomes:
measure: To determine the change of proviral HIV-1 DNA from baseline to month 3
timeFrame: 3 months
measure: 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
timeFrame: 9 months
measure: To quantify plasma HIV (limit of detection 2 copies/ml of plasma)
timeFrame: 9 months
measure: To quantify cell associated HIV RNA (unspliced and multiply spliced) in resting and activated CD4+ T cells
timeFrame: 9 months
measure: To determine the decay characteristics of HIV in resting CD4+ T cells by quantitative co-culture assays
timeFrame: 9 months
measure: To determine the half-life of HIV in resting CD4+ T cells
timeFrame: 9months
measure: To carry out phylogenetic analysis of HIV in the plasma, resting, and activated CD4+ T cell compartments
timeFrame: 9 months
measure: 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)
timeFrame: 9 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic
state: Ontario
Study officials:
affiliation: University of Toronto
name: Colin Kovacs, MD
role: PRINCIPAL_INVESTIGATOR
References: