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Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02961829
First Posted: November 11, 2016
Last Update Posted: November 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico
ViiV Healthcare
Information provided by (Responsible Party):
Ricardo Sobhie Diaz, MD, PHD, Federal University of São Paulo
  Purpose
It is becoming clear that a combination of interventions will be desirable to achieve HIV cure. Therefore the investigators propose a pilot proof of concept study, using combination of a number of different interventions for eradicating residual plasma viremia and decreasing HIV reservoirs. The investigators hypothesize that, (i) antiretroviral intensification using Maraviroc, and/or dolutegravir with (ii) Dendritic Cell vaccination using autologous HIV, and (iii) purging intervention using the Class III HDACs, Sirtuin-1, and (iv) decreasing the ratio of long-lived central memory (TCM)/transitional memory (TTM) CD4+ T-cells using Auranofin will provide a synergistic impact leading to a sterilizing cure of HIV infection. Results of this study may provide insightful evidence for planning the next steps using the more efficacious combination of intervention strategies towards HIV sterilizing cure.

Condition Intervention
Chronic Infection HIV Drug: Maraviroc Drug: Dolutegravir Biological: Dendritic Cell Vaccine Drug: Auranofin Drug: Sirtuin Histone deacetylase inhibitor

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure

Resource links provided by NLM:


Further study details as provided by Ricardo Sobhie Diaz, MD, PHD, Federal University of São Paulo:

Primary Outcome Measures:
  • Ultrasensitive RNA Viral load, [ Time Frame: from baseline and every 4 weeks up to 48 weeks. ]
  • Cell-associated HIV RNA [ Time Frame: from baseline and every 4 weeks up to 48 weeks. ]
  • Episomal DNA [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • specific HIV antibodies [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • CD38 and HLA-DR on CD4 and CD8+ cells [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]
  • PBMC for env sequence evolution [ Time Frame: from baseline and every 4 weeks up to 48 weeks ]

Enrollment: 30
Study Start Date: July 2015
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Antiretroviral Treated (ART) Group
Five patients will receive no further intervention this group (control group)
Experimental: ART Intensification Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks
Drug: Maraviroc
antiretroviral intensification
Other Names:
  • Selzentry
  • Celsentri
Drug: Dolutegravir
antiretroviral intensification
Other Name: Tivicay
Experimental: ART Intensification + Nicotinamide Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.
Drug: Maraviroc
antiretroviral intensification
Other Names:
  • Selzentry
  • Celsentri
Drug: Dolutegravir
antiretroviral intensification
Other Name: Tivicay
Drug: Sirtuin Histone deacetylase inhibitor
latency disruption
Other Name: Nicotinamide
Experimental: ART Intensification + Auranofin Group
Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.
Drug: Maraviroc
antiretroviral intensification
Other Names:
  • Selzentry
  • Celsentri
Drug: Dolutegravir
antiretroviral intensification
Other Name: Tivicay
Drug: Auranofin
purging
Other Name: Gold Salt
Experimental: ART Intensification + DC vaccine Group
Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine.
Drug: Dolutegravir
antiretroviral intensification
Other Name: Tivicay
Biological: Dendritic Cell Vaccine
Therapeutic vaccination
Other Name: DC Vaccine
Experimental: Multi Interventional Group
Five patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.
Drug: Dolutegravir
antiretroviral intensification
Other Name: Tivicay
Biological: Dendritic Cell Vaccine
Therapeutic vaccination
Other Name: DC Vaccine
Drug: Auranofin
purging
Other Name: Gold Salt
Drug: Sirtuin Histone deacetylase inhibitor
latency disruption
Other Name: Nicotinamide

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • > 18 years old Documented HIV-1 infection.
  • Has voluntarily signed ICF.
  • On HAART ≥ 2 years, without changes in the 24 weeks immediately prior to screening.
  • HIV viral load <50 copies/mL, and never > 50 copies/mL on 2 consecutive occasions in the last 2 years. CD4 count nadir.
  • > 350 cells/ mm3 Current CD4 count > 500 cells/ mm3.
  • R5 HIV-1 at Screening as defined by proviral DNA genotropism.

Exclusion Criteria:

A subject will NOT be eligible for study participation if he/she meets ANY of the following criteria:

  • Any evidence of an active AIDS-defining condition.
  • Any significant acute medical illness in the past 8 weeks.
  • Women who are pregnant or breastfeeding.
  • Use of any of the following within 90 days prior to entry: systemic cytotoxic chemotherapy; investigational agents; immunomodulators (colony-stimulating factors, growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons); coumadin, warfarin, or other Coumadin derivative anticoagulants. Use of an agent definitely or possibly associated with effects on QT intervals: amiodarone, arsenic trioxide, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, probucol, procainamide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine.
  • Receipt of compounds with HDAC inhibitor-like activity, such as valproic acid or nicotinamide within the last 30 days. Potential participants may enroll after a 30-day washout period.
  • Known hypersensitivity to the components of gold salt, nicotinamide or its analogs.
  • Hepatitis B (HBsAg +) or Hepatitis C (HCV RNA +) infection.
  • Known renal insufficiency defined as calculated creatinine clearance (Cockcroft Gault formula) <60 mL/min.
  • Subjects with a laboratory abnormality grade 3 or 4 with the following exceptions: pancreatic amylase, cholesterol, triglyceride, gamma glutamyl transpeptidase, bilirubin.
  • Any condition which, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02961829


Locations
Brazil
CCDI
Sao Paulo, SP, Brazil, 04040002
Sponsors and Collaborators
Federal University of São Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico
ViiV Healthcare
  More Information

Responsible Party: Ricardo Sobhie Diaz, MD, PHD, Associate Professor of Medicine, Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT02961829     History of Changes
Other Study ID Numbers: SPARC-7
First Submitted: December 18, 2015
First Posted: November 11, 2016
Last Update Posted: November 8, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Ricardo Sobhie Diaz, MD, PHD, Federal University of São Paulo:
Dendritic Cell vaccination using
antiretroviral intensification
Auranofin
Histone Deacetylase Inhibitor
residual viral replication
HIV sanctuaries
HIV latency

Additional relevant MeSH terms:
Vaccines
Maraviroc
Dolutegravir
Niacinamide
Niacin
Nicotinic Acids
Histone Deacetylase Inhibitors
Auranofin
Immunologic Factors
Physiological Effects of Drugs
CCR5 Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Vasodilator Agents
Antirheumatic Agents