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

July 25, 2020 updated by: Ricardo Sobhie Diaz, MD, PHD, Federal University of São Paulo
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • Sao Paulo, SP, Brazil, 04040002
        • CCDI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Celsentri
  • Selzentry
Drug: Dolutegravir
antiretroviral intensification
Other Names:
  • 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:
  • Celsentri
  • Selzentry
Drug: Dolutegravir
antiretroviral intensification
Other Names:
  • Tivicay
Drug: Sirtuin Histone deacetylase inhibitor
latency disruption
Other Names:
  • 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:
  • Celsentri
  • Selzentry
Drug: Dolutegravir
antiretroviral intensification
Other Names:
  • Tivicay
Drug: Auranofin
purging
Other Names:
  • 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 Names:
  • Tivicay
Biological: Dendritic Cell Vaccine
Therapeutic vaccination
Other Names:
  • 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 Names:
  • Tivicay
Drug: Sirtuin Histone deacetylase inhibitor
latency disruption
Other Names:
  • Nicotinamide
Drug: Auranofin
purging
Other Names:
  • Gold Salt
Biological: Dendritic Cell Vaccine
Therapeutic vaccination
Other Names:
  • DC Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Ultrasensitive RNA Viral load,
Time Frame: from baseline and every 4 weeks up to 48 weeks.
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.
from baseline and every 4 weeks up to 48 weeks.
Episomal DNA
Time Frame: from baseline and every 4 weeks up to 48 weeks
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
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
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
from baseline and every 4 weeks up to 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federal University of São Paulo

Collaborators

Fundação de Amparo à Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico
ViiV Healthcare

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2015

Primary Completion (ACTUAL)

March 1, 2019

Study Completion (ACTUAL)

March 1, 2020

Study Registration Dates

First Submitted

December 18, 2015

First Submitted That Met QC Criteria

November 9, 2016

First Posted (ESTIMATE)

November 11, 2016

Study Record Updates

Last Update Posted (ACTUAL)

July 28, 2020

Last Update Submitted That Met QC Criteria

July 25, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPARC-7

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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