Immune Activation in HIV-1 Infected Patients Under AntiRetroviral Treatment (ACTIVIH)

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

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).

Study Overview

• Status: Completed
• Conditions: Immune Deficiency; Other Diagnoses, Comorbidities, and Complications; HIV-related Gut Disease - Cause Unknown; Activation of Latent Virus
• Intervention / Treatment: Biological: Blood test

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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • University hospital Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treated HIV-1 infected patients; Treated HIV-1 infected patients for Blood test	Biological: Blood test; Blood test
Experimental: No treated HIV-1 infected patients; No treated HIV-1 infected patients for Blood test	Biological: Blood test; Blood test
Experimental: Healthy witness; Healthy witness for Blood test	Biological: Blood test; Blood test

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
No immunological response to treatment	Measurement of circulating CD4 +	No immunological response to treatment the day of inclusion
Renal Review	Estimated glomerular filtration rate, Na / K / Cl / alkaline reserve, blood uric acid, typing with proteinuria, albuminuria, creatinine, phosphorus reabsorption, urine dipstick	Renal Review the day of inclusion
Bone balance	Determination of Calcium and phosphate levels in fasting, PTH, TSH, 25hydroxy vitamin D, testosterone (male), estradiol (female)	Bone balance the day of inclusion
Metabolic syndrome assessment	Metasting blood glucose, HbA1c, triglycerides, LDL cholesterol, HDL cholesterol	Metabolic syndrome assessment the day of inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: JACQUES REYNES, PU PH, Univerty Hospital Montpellier

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: January 6, 2015
• First Posted (Estimate): January 8, 2015

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 19, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: 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
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes
• Other Study ID Numbers: 9187