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

• Conditions: HIV Infection; Tuberculosis Infection
• Interventions: Other: Detection of molecular Biomarkers

• Registration Number: NCT03941210
• Lead Sponsor: ANRS, Emerging Infectious Diseases

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-01
• Study First Submitted: 2019-05-06
• Study First Submitted QC: 2019-05-06
• Study First Posted: 2019-05-07
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-06
• Last Update Posted: 2020-01-07
• Primary Completion: 2020-03-01
• Study Completion: 2020-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

Not provided

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HIV+/TB+	Detection of molecular Biomarkers	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
HIV+/TB-	Detection of molecular Biomarkers	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
HIV-/TB-	Detection of molecular Biomarkers	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.
HIV-/TB+	Detection of molecular Biomarkers	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

Primary Outcome Measures

Name	Time	Method
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	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.

Trial Locations

Locations (1)

Institut Pasteur du Cambodge; 🇰🇭 Phnom Penh, Cambodia