Clinical trial NCT02269605: Bryostatin-1 Effect on HIV-1 Latency and Reservoir in HIV-1 Infected Patients Receiving Antiretroviral Treatment
Official title: Bryostatin-1 Effect on HIV-1 Latency and Reservoir HIV-1 Infected Patients Receiving Antiretroviral Treatment: Pilot, Controlled, Double Blinded, Dose Searching Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Keywords: HIV reservoir
Bryostatin
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2014-10-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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:

* 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.

Primary outcomes:
measure: Intracellular HIV-1 RNA (usRNA and msRNA) level before and after bryostatin-1 administration
timeFrame: Baseline visit and days 2 and 3 after the day of treatment
Secondary outcomes:
measure: HIV-1 RNA level
timeFrame: 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
measure: CD4+ and CD8+ T (CD38+ and HLA DR+ positive) cell level
timeFrame: Baseline visit, day 1 and day 3
measure: Episomal DNA with 2 LTRs level
timeFrame: Baseline visit, day 1 and day 3
measure: Adverse Events
timeFrame: From baseline visit to day 28 after drug administration
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Infectious Diseases Service
state: Non US/Canada
Study officials:
affiliation: Hospital Universitario Ramón y Cajal
name: Santiago Moreno, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1128/jvi.77.3.1659-1665.2003. No abstract available.
citation: 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. doi: 10.1001/jama.288.2.162-a. No abstract available.
citation: 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.
citation: Gutierrez C, Serrano-Villar S, Madrid-Elena N, Perez-Elias MJ, Martin ME, Barbas C, Ruiperez J, Munoz E, Munoz-Fernandez MA, Castor T, Moreno S. Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy. AIDS. 2016 Jun 1;30(9):1385-92. doi: 10.1097/QAD.0000000000001064.