BRYOLAT: Bryostatin-1 Effect on HIV-1 Latency and Reservoir in HIV-1 Infected Patients Receiving Antiretroviral Treatment
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Group 1 Patients receiving placebo (sodium chloride) at single dose |
Other: Placebo
Group 1: Placebo (sodium chloride 0.8 %) at single dose
|
| Active Comparator: Group 2 Patients receiving Bryostatin 1 (10ug/m2) at single dose |
Drug: Bryostatin 1 (10ug/m2)
Group 2: Bryostatin 1 (10ug/m2) at single dose
|
| Active Comparator: Group 3 Patients receiving Bryostatin 1 (20ug/m2) at single dose |
Drug: Bryostatin 1 (20ug/m2)
Group 3: Bryostatin 1 (20ug/m2) at single dose
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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:
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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
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Infectious Diseases Service | Madrid | Non US/Canada | Spain | 28034 |
Sponsors and Collaborators
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Investigators
- Principal Investigator: Santiago Moreno, MD, PhD, Hospital Universitario Ramón y Cajal
Study Documents (Full-Text)
None provided.More Information
Publications
- Blankson JN, Gallant JE, Quinn TC, Bartlett JG, Siliciano RF. Loss of HIV-1-specific immunity during treatment interruption in 2 chronically infected patients. JAMA. 2002 Jul 10;288(2):162-4.
- Persaud D, Zhou Y, Siliciano JM, Siliciano RF. Latency in human immunodeficiency virus type 1 infection: no easy answers. J Virol. 2003 Feb;77(3):1659-65. Review.
- Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009 Mar 6;323(5919):1304-7. doi: 10.1126/science.1165706. Review.
- BRYOLAT