Immune Activation in HIV-1 Infected Patients Under AntiRetroviral Treatment

Study Overview
=================
Brief Summary
-----------------
Immune Activation persists in HIV-1 infected patients despite efficient antiretroviral treatment. This immune activation is responsible for immune deficiency as well as for non-AIDS related comorbidities, such as non-alcoholic Fatty liver disease, metabolic syndrome or osteoporosis. The goal of this observational transversal multicentric study is to establish the etiologic factors of persistent immune activation in treated HIV-1 infected patients (persistent de novo infection of T CD4+ cells, microbial translocation, active coinfections, immunosenescence, T CD4+ cells lymphopenia, Treg deficiency), its different forms ( activation of T CD4+ cells, T CD8+ cells, B cells, NK cells, monocytes, granulocytes, platelets, endothelial cells or general inflammation) and the potential correlation between causes, forms of immune activation and emergent comorbidities (kidney, bone or liver dysfunction, metabolic syndrome).

Detailed Description
-----------------
Immune Activation persists in HIV-1 infected patients despite efficient antiretroviral treatment. This immune activation is responsible for immune deficiency as well as for non-AIDS related comorbidities, such as non-alcoholic Fatty liver disease, metabolic syndrome or osteoporosis. The goal of this observational transversal multicentric study is to establish the etiologic factors of persistent immune activation in treated HIV-1 infected patients (persistent de novo infection of T CD4+ cells, microbial translocation, active coinfections, immunosenescence, T CD4+ cells lymphopenia, Treg deficiency), its different forms ( activation of T CD4+ cells, T CD8+ cells, B cells, NK cells, monocytes, granulocytes, platelets, endothelial cells or general inflammation) and the potential correlation between causes, forms of immune activation and emergent comorbidities (kidney, bone or liver dysfunction, metabolic syndrome). These correlations could highlight physiopathologic mechanisms relating a specific cause of immune activation, activation of a specific subpopulation of immune cells and a comorbidity. Physiopathologic mechanisms could then be tested in vitro and lead into new therapeutic tracks of immune activation secondary to HIV-1 or to the natural ageing process.

Official Title
-----------------
Immune Activation in HIV-1 Infected Patients Under AntiRetroviral Treatment: Etiologic Factors, Forms and Potential Association With Chronic Comorbidities Unrelated to Immune Deficiency.

Conditions
-----------------
Immune Deficiency, HIV-related Gut Disease - Cause Unknown, Activation of Latent Virus, Other Diagnoses, Comorbidities, and Complications

Intervention / Treatment
-----------------
* Biological: Blood test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Age > or = 45 years HIV-1 infection Number of T CD4+ lymphocytes before antiretroviral treatment < 350 cells/mm3 Current number of T CD4+ lymphocytes > 200 cells / mm3 for 6 moths before inclusion Efficient and well tolerated antiretroviral treatment for more than 24 months HIV-1 viral load < 50 copies/ml for more than 24 months before inclusion Patient able to understand the nature, the objective and the methods of the study Patient having signed the informed consent Affiliation to French Social Security System Exclusion criteria: Patient having a current evidence of II to IV rank of the ANRS scale clinical condition Patient having a current evidence of III to IV rank of the ANRS scale biological condition Patient has a current evidence of an active coinfection Patient has a current (active) diagnosis of acute hepatitis due to any cause. Patients with chronic hepatitis, including chronic hepatitis B and/or C, may enter the study as long as they have stable liver function tests and undetectable viral load of hepatitis B and/or C Patient has a cirrhosis Patient presents with a non infectious pathology that might give immune modifications Patient using immuno-modulator therapy or chemotherapy Patient is currently participating or has participated in a study (within the exclusion period defined by this study) Patient is pregnant or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated HIV-1 infected patients<br>Treated HIV-1 infected patients for Blood test | Biological: Blood test<br>* Blood test<br>|
| Experimental: No treated HIV-1 infected patients<br>No treated HIV-1 infected patients for Blood test | Biological: Blood test<br>* Blood test<br>|
| Experimental: Healthy witness<br>Healthy witness for Blood test | Biological: Blood test<br>* Blood test<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infection of novo persistent | Etiologic factors of persistent immune activation in treated HIV-1 infected patients (obstinacy of the infection of new cells T CD4 +, microbial translocation, active coinfection, immunosenescence, lymphopenia T CD4 +, deficit in lymphocytes Treg) on a day: the day of the inclusion | Infection of novo persistent the day of inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbial translocation | Microbial translocation (DNA bacterial plasma derivative) | Microbial translocation the day of inclusion | 
| Diagnosis immunizing activation | Activation T CD4 and T CD8, B, NK | Diagnosis immunizing activation the day of inclusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune Activation, HIV-1 infected subjects, Undetectable viral load, Causes of Immune Activation in HIV-1 infected patients, Forms of Immune Activation, Emergent non-AIDS related comorbidities