Micro RNA as Prediction and/or Prognostic Markers of IRIS in TB-HIV Co-infected Patients (miRNA)

January 6, 2020 updated by: ANRS, Emerging Infectious Diseases

The role of miRNAs in HIV disease is yet to be completely defined. Host miRNAs target certain HIV genes, thus can affect HIV replication and participate in viral control. miRNAs can also block HIV production through disruption of Gag assembly on cell membranes. miRNA expression can characterize HIV disease phenotype, as has been shown in HIV elite controllers who have a well-defined miRNA expression profile. However, the studies of miRNA in acute infection and co-infections like tuberculosis are lacking. The investigators showed that during immune reconstitution syndrome (IRIS) in HIV/TB coinfected patients, innate immune response play a role as through NK cell degranulation, therefore testing for this could be used as a predictive marker of IRIS.

One of the limitations of miRNA detection is the technique, which is time-consuming, and needs laboratories that are specialized and equipped for molecular biology techniques. In contrast, flow cytometry has been developed in routine labs and has well-standardized techniques. For the routine detection of miRNA, flow cytometry could be the best way to perform high throughput screening for clinical applications.

Flow cytometry is a simple and effective way to evaluate miRNAs expression. In this project the investigators propose to evaluate, using flow cytometry, whether circulating miRNA pattern might be applicable as potential biomarkers in prediction and prognosis of IRIS in HIV/TB co-infected patients. The investigators propose to study the miRNA expression profile in a cohort of patients with a HIV infection and Tuberculosis and correlate it with their clinical evolution. As controls, the investigators propose to analyze expression of miRNAs in healthy controls as well as TB and HIV mono-infected patients.

AIMS OF THE PROPOSAL

  1. Identify miRNA expression profile as potential novel predictive and prognostic biomarkers for IRIS.
  2. Identify the miRNA expression profile in HIV patients, in TB patients and in HIV/TB co-infected patients.

Study Overview

Status

Unknown

Study Type

Observational

Enrollment (Anticipated)

134

Contacts and Locations

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

Study Contact

Study Locations

      • Phnom Penh, Cambodia
        • Recruiting
        • Institut Pasteur du Cambodge
        • Contact:

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 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

  1. 74 TB - HIV co-infected patients (37 TB-IRIS and 37 non TB-IRIS) whose plasma were stored during the ANRS 12095 CAMELIA clinical trial (NCT00226434) and ANRS 12153 CAPRI NK study will be included in the study.
  2. 20 HIV ART naïve patients will be enrolled in Sihanouk Hospital Center of HOPE in Cambodia.
  3. 20 newly active tuberculosis patients will be enrolled in Sihanouk Hospital Center of HOPE in Cambodia.
  4. 20 healthy individuals will be recruited from the patients coming to Pasteur Institute in Cambodia for pre-marital test for HIV and who agree to participate in the study.

Description

For HIV+/TB+ participants:

Inclusion Criteria

  • cf the CAMELIA clinical trial (NCT00226434)

Exclusion Criteria:

  • cf the CAMELIA clinical trial (NCT00226434)

For HIV+/TB- participants:

Inclusion Criteria

  • Age ≥ 18 years
  • HIV+
  • CD4 cell count ≤ 200 x 106 cells/l
  • No evidence of tuberculosis infection.

Exclusion Criteria:

  • Age <18 years
  • Pregnancy or breastfeeding
  • CD4 cell count > 200 x 106 cells/l
  • Evidence of tuberculosis infection
  • Non ART naive at inclusion

For HIV-/TB+ participants:

Inclusion Criteria

  • Age ≥ 18 years
  • HIV-
  • Confirmed tuberculosis infection.

Exclusion Criteria:

  • Age <18 years
  • Pregnancy or breastfeeding
  • AFB negative or MTB/RIF negative for MTB,
  • History of TB infection
  • HIV+

For HIV-/TB- participants:

Inclusion Criteria

  • Age ≥ 18 years
  • HIV-
  • No evidence of tuberculosis infection.

Exclusion Criteria:

  • Age <18 years
  • Pregnancy or breastfeeding
  • Evidence of tuberculosis infection
  • HIV+

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HIV+/TB+

Frozen samples and data from participants recruited in the ANRS 12095 CAMELIA clinical trial and the ANRS 12153 CAPRI NK study will be used for this study arm

All plasma samples were collected before any treatment during IRIS diagnosis and at W8 post TB treatment initiation

MicroRNA expression profile analysis by flow cytometry
HIV+/TB-

Participants included in this study arm will be HIV+ and TB-

One time collection of 5 ml of blood will be drawn in EDTA tube for each patient before starting cART and sent to the laboratory for protocol analysis

MicroRNA expression profile analysis by flow cytometry
HIV-/TB+

Participants included in this study arm will be HIV- and TB+

Collection of 5 ml of blood drawing in EDTA tube will be requested for each patient before starting TB drug treatment and after week 2 and 8 of treatment

MicroRNA expression profile analysis by flow cytometry
HIV-/TB-

Participants included in this study arm will be HIV- and TB-

Clinical examination to rule out overt evidence of TB and, whenever needed, routine TB testing as per national guidelines (sputum smear ± chest X-ray) in case of symptoms/clinical manifestations suggestive of TB.

MicroRNA expression profile analysis by flow cytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
miRNA expression profile in a cohort of patients with a HIV infection and Tuberculosis and correlate it with their clinical evolution
Time Frame: March 1st 2018 - March 1st 2020

Evaluate, using flow cytometry, whether circulating miRNA (in plasma and/or exosomes) pattern might be applicable as potential biomarkers in prediction and prognosis of IRIS in HIV/TB co-infected patients.

Description of miRNA expression profile in a cohort of patients with a HIV infection and Tuberculosis and correlate it with their clinical evolution.

March 1st 2018 - March 1st 2020

Collaborators and Investigators

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

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)

March 1, 2018

Primary Completion (Anticipated)

March 1, 2020

Study Completion (Anticipated)

March 1, 2020

Study Registration Dates

First Submitted

May 6, 2019

First Submitted That Met QC Criteria

May 6, 2019

First Posted (Actual)

May 7, 2019

Study Record Updates

Last Update Posted (Actual)

January 7, 2020

Last Update Submitted That Met QC Criteria

January 6, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

Clinical Trials on HIV Infection

Clinical Trials on Detection of molecular Biomarkers

3
Subscribe