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

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

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

Conditions
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HIV Infection, Tuberculosis Infection

Intervention / Treatment
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* Other: Detection of molecular Biomarkers


Participation Criteria
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Eligibility Criteria
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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+

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV+/TB+<br>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 | Other: Detection of molecular Biomarkers<br>* MicroRNA expression profile analysis by flow cytometry<br>|
| HIV+/TB-<br>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 | Other: Detection of molecular Biomarkers<br>* MicroRNA expression profile analysis by flow cytometry<br>|
| HIV-/TB+<br>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 | Other: Detection of molecular Biomarkers<br>* MicroRNA expression profile analysis by flow cytometry<br>|
| HIV-/TB-<br>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. | Other: Detection of molecular Biomarkers<br>* MicroRNA expression profile analysis by flow cytometry<br>|

What is the study measuring?
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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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microRNA, HIV, Tuberculosis, IRIS, Biomarkers