Bryostatin-1 Effect on HIV-1 Latency and Reservoir in HIV-1 Infected Patients Receiving Antiretroviral Treatment

Study Overview
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Brief Summary
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Phase I, randomized, double blind, placebo-controlled, dose-finding trial. The trial´s goal is to evaluate two different doses of Bryostatin on HIV-1 latency and reservoir in HIV-1 infected patients receiving antiretroviral treatment.

Official Title
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Bryostatin-1 Effect on HIV-1 Latency and Reservoir HIV-1 Infected Patients Receiving Antiretroviral Treatment: Pilot, Controlled, Double Blinded, Dose Searching Trial

Conditions
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HIV Infection

Intervention / Treatment
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* Other: Placebo
* Drug: Bryostatin 1 (10ug/m2)
* Drug: Bryostatin 1 (20ug/m2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients understanding the trial purpose Patients between 18 and 50 years of age Patients with chronic HIV-1 infection Patients receiving antiretroviral treatment with at least 3 active drugs for at least 2 years Undetectable viral load measured by ultra sensitive methods CD4+ levels higher than 350 cells/mm3 Patients committed to use contraceptive methods during the trial and up to 3 months after. Exclusion Criteria: Previous antiretroviral treatment failure, as any viral load outbreak after having had undetectable HIV-1 load. Low grade, transitory outbreaks (<200 RNA copies/ml) resolved without treatment modifications are excluded Patients planned to interrupt antiretroviral treatment during the trial Patients receiving immunosuppressant or immunostimulant drugs, including valproic acid. Pregnant women Bryostatin-1 hypersensitivity Being enrolled in another clinical trial or having participated in another clinical trial in the previous 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1<br>Patients receiving placebo (sodium chloride) at single dose | Other: Placebo<br>* Group 1: Placebo (sodium chloride 0.8 %) at single dose<br>|
| Active Comparator: Group 2<br>Patients receiving Bryostatin 1 (10ug/m2) at single dose | Drug: Bryostatin 1 (10ug/m2)<br>* Group 2: Bryostatin 1 (10ug/m2) at single dose<br>|
| Active Comparator: Group 3<br>Patients receiving Bryostatin 1 (20ug/m2) at single dose | Drug: Bryostatin 1 (20ug/m2)<br>* Group 3: Bryostatin 1 (20ug/m2) at single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracellular HIV-1 RNA (usRNA and msRNA) level before and after bryostatin-1 administration |  | Baseline visit and days 2 and 3 after the day of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 RNA level |  | Baseline visit, day 0 (15, 30, 60 minutes after begining of drug administration and 1, 2, 4, 8, 12 hours after begining of drug administration) and days 1, 2 and 3 | 
| CD4+ and CD8+ T (CD38+ and HLA DR+ positive) cell level |  | Baseline visit, day 1 and day 3 | 
| Episomal DNA with 2 LTRs level |  | Baseline visit, day 1 and day 3 | 
| Adverse Events |  | From baseline visit to day 28 after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV reservoir, Bryostatin