Fuzeon Viral Decay Pilot Study

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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HIV-1

Intervention / Treatment
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* Drug: enfuvirtide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be HIV infected Patient must be > 18 years old Patient must be taking standard combination antiretroviral therapy with 2-3 NRTIs and 1-2 PIs or a NNRTIs for at least five years 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 Patient must have a CD4 count above 400 cells/mm3 in last 3 months Female patient must agree to use two methods of birth control or abstinence during the period of the study Patient has to have signed full informed consent Exclusion Criteria: Patient who would have difficulty participating in a trial due to non-adherence or substance abuse Patient who have taken mono or dual antiretroviral therapy Patient who have had a viral load > 50 copies/mL on any antiretroviral regimen 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 Patient with a malignancy Patient with other significant underlying disease (non-HIV) that might impinge upon disease progression or death Patient with an active AIDS-defining illnesses in the past six months Patients who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Did not receive enfuvirtide<br>patients were randomized to either receive enfuviratide or not receive it | Drug: enfuvirtide<br>* 1ml BID<br>|
| Active Comparator: enfuvirtide<br>enfuvirtide 1ml BID | Drug: enfuvirtide<br>* 1ml BID<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fuzeon, Viral Decay