Viral Biofilms: Hijacking T Cell Extracellular Matrix to Regulate HIV-1 Spread? (TRANSBioHIV)

February 26, 2018 updated by: ANRS, Emerging Infectious Diseases
This project aims at characterizing HIV-1 viral biofilms structural and functional properties and at deciphering its role as a new viral reservoir and as a new mode of viral spread. The prospective national study will be conducted on cells isolated from blood samples from 20 patients infected with HIV.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators' preliminary data indicate that besides " free " infectious viral particles, HIV-1 infected cluster of differentiation 4 (CD4+) lymphocytes also produce extracellular viral assemblies wrapped in an extracellular matrix cocoon and tightly bound to the surface of the cell. Importantly, these structures are infectious, transferred to target cells upon intercellular contacts and they are key role in HIV-1 spread between T lymphocytes. HIV-1 viral biofilm could be important not only for direct transmission of the virions but also for " trans-infection ", a process our objectives are:

  • to better characterize the molecular composition and the architecture of this biofilm (using proteomics, glycomic superresolution cell imaging approaches) with regard to its properties (infectivity, adhesiveness, protection of virions) and to determine whether cells from infected patients produce such structures.
  • to delineate the viral factors regulating the formation of these new infectious structures (with a particular attention on Tat, Vpu and Nef HIV-1 encoded using mutant viruses or expression vectors).
  • to investigate the lymphocyte pathways regulating the viral biofilms formation and composition in extracellular matrix (ECM) proteins (using quantitative polymerase chain reaction (qPCR) and siRNA).
  • to determine whether those viral biofilms are involved in HIV-1 transmission by transinfection
  • to study the contribution of those infectious structures and the dynamics of their transmission in lymph nodes.

This project may contribute to decipher the role of viral biofilms in HIV-1 transmission. Ultimately, we intend to determine how the interference of retroviral infections with T cell activation pathways modulates the pattern of ECM production by T cells, tuning viral biofilm composition and regulating viral dissemination.

Study Type

Interventional

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

  • France
      • Le Kremlin Bicêtre, France, 94270
        • Service de Médecine Interne, CHU Kremlin-Bicêtre

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • able to give written consent
  • HIV positive serology HIV1
  • Viral load > 10 000 copies/ml
  • CD4 T cells > 100 cells/mm3
  • or Treated by antiretroviral therapy (ARV) for less than 6 months
  • Covered by French Social Security

Exclusion Criteria:

  • Involved in a clinical trial
  • Pregnancy (inclusion can be postponed)
  • No covered by French Social Security

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: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HIV infection
20 HIV infected subjects
Other: Blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The percentage of HIV positive patients with cells producing biofilms.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
The number of cells with biofilms identified among the HIV positive patients presenting such structures.
Time Frame: 2 years
2 years

Collaborators and Investigators

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

Sponsor

ANRS, Emerging Infectious Diseases

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)

January 1, 2013

Primary Completion (Actual)

February 1, 2018

Study Completion (Actual)

February 1, 2018

Study Registration Dates

First Submitted

July 2, 2013

First Submitted That Met QC Criteria

July 8, 2013

First Posted (Estimate)

July 11, 2013

Study Record Updates

Last Update Posted (Actual)

February 27, 2018

Last Update Submitted That Met QC Criteria

February 26, 2018

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS RF001 TRANSBioHIV

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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