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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Federal University of São Paulo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 9, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 11, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 28, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings