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

NCT ID: NCT03941210

Last Updated: 2020-01-07

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 134 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2020-03-01

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.

Conditions

HIV Infection; Tuberculosis Infection

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

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

Detection of molecular Biomarkers

Intervention Type: OTHER

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

Detection of molecular Biomarkers

Intervention Type: OTHER

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

Detection of molecular Biomarkers

Intervention Type: OTHER

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.

Detection of molecular Biomarkers

Intervention Type: OTHER

MicroRNA expression profile analysis by flow cytometry

Interventions

Detection of molecular Biomarkers

MicroRNA expression profile analysis by flow cytometry

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• cf the CAMELIA clinical trial (NCT00226434)

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

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

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

Exclusion Criteria

• cf the CAMELIA clinical trial (NCT00226434)

For HIV+/TB- participants:

• 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:

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

For HIV-/TB- participants:

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut Pasteur du Cambodge

Phnom Penh, , Cambodia

Site Status: RECRUITING

Countries

Cambodia

Central Contacts

Polidy PEAN, MD, PhD

Role: CONTACT

polidy@pasteur-kh.org

+85512552182

Facility Contacts

Polidy PEAN, MD, PhD

Role: primary

polidy@pasteur-kh.org

+85512552182

Other Identifiers

ANRS 12358

Identifier Type: -

Identifier Source: org_study_id