the " Extreme " Cohort (CODEX)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01520844
First received: August 9, 2011
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

Two cohorts of patients with a phenotype of HIV resistance exist in France. The ANRS CO15 ALT cohort was set up in 1994. 71 patients were enrolled defined on immunological criteria: CD4 T cell count above 600/mm3 with a stable or increasing count (positive or zero slopes) on at least three consecutive exams performed during the last 5 years whatever the viral load was, with a known HIV infection for at least 8 years. A consortium of research teams has studied the immunovirological characteristics of these patients. After 16 years of follow-up, 6 patients are still actively followed. The main results have shown the lack of deletion in viral genes nor any functional viral defects, a small size for the viral reservoir, and distinctive genetic characteristics of the host (HLA, chemokines) which lead to potent immune cell responses associated with virus control.

The ANRS CO18 HIV Controller cohort set up in 2009 is stemming from the French National Observatory of HIV Controllers which was active between 2006 and 2008 (Study ANRS EP36). 152 patients are enrolled who are defined on virological criteria: the last 5 plasmatic viral loads should be below 400 copies/mL without any antiretroviral treatment, in HIV-infected patients for more than 5 years. A consortium of research teams has studied these patients and has shown that Controllers are infected with replication-competent HIV, that HIV infects CD4 T cells but that the viral replication in CD4 T cells is fully controlled by CD8 T cells.

The main objective is to gather in common cohort patients with a particular resistance to HIV infection, either with an immunological control (ALT), either a virological control (HIV Controllers). The enrolled patients will be the patients already enrolled in the cohorts CO15 and CO18 and new patients. This will allow common physiopathological studies to precise the mechanisms leading to the virus control and CD4 homeostasis. A better knowledge of the mechanisms of viral control and immune response preservation is very important in the setting of vaccine perspectives. This cohort will allow common research projects with common fundings and a better visibility both for clinicians who see patients with unusual phenotypes and for international research. Such a cohort will be unique in the world by its size and the presence of these two complementary groups of patients. The two main objectives for the " Extreme " cohort (CODEX) are clinical and immunovirological. The investigators wish to precise the impact of a prolonged untreated HIV infection, to describe the frequency of the "immunological escapes" (CD4 T cell decrease) or "virological escapes" (permanent or transient viral load increase). The investigators wish to study the genetic characteristics of the patients and those of their viruses, the innate and adaptative immune responses directed against HIV and other viruses, the consequences of inflammation, and the characteristics of the loss of control.


Condition Intervention
HIV Infection
Biological: blood sampling

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Multicentric Cohort of HIV Patient With Extrem Profil

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • clinical and immuno-virological [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • mechanisms leading to the virus control and CD4 homeostasy with physiopathological studies [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • impact of a prolonged untreated HIV infection, [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • frequency of the "immunological escapes" (CD4 T cell decrease) or "virological escapes" (permanent or transient viral load increase) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • genetic characteristics of the patients and those of their viruses, the innate and adaptative immune responses directed against HIV and other viruses, the consequences of inflammation, and the characteristics of the loss of control [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: February 2012
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 0 Biological: blood sampling
blood sampling

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 at enrollment
  • Able to give written consent
  • Covered by French Social Security
  • accept the constraints imposed by the study
  • without antiretroviral therapy

ALT group: Documented HIV-1 seropositive for at least 8 years with a CD4 count above 600/mm3 with a rate stable or increasing (positive or zero slope) on at least three consecutive examinations performed during the last 5 years regardless of the viral load in the absence of antiretroviral treatment

HIC group: HIV-1 Seropositivity known for at least five years, asymptomatic, with the last 5 viral loads in HIV-RNA consecutive <400 copies / mL regardless of CD4 count in the absence of antiretroviral treatment

ALT HIC group: HIV-1 seropositive known for at least 8 years and CD4 cell counts greater than 600/mm3 with a rate stable or increasing (positive or zero slope) on at least three consecutive examinations performed during the last 5 years and with the last 5 viral loads in HIV-RNA consecutive <400 copies / mL in the absence of antiretroviral therapy.

Exclusion Criteria:

Under protection(saving) of justice

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520844

Contacts
Contact: Olivier Lambotte, Professor 01 49 59 67 54 olivier.lambotte@bct.aphp.fr
Contact: Faroudy Boufassa 01 45 21 23 65 faroudy.boufassa@inserm.fr

Locations
France
Lambotte Recruiting
Kremlin Bicetre, France
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Olivier Lambotte, Professor Kremlin Bicetre
Study Chair: Laurence Meyer, Professor Methodologist INSERM CESP U1018
  More Information

No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT01520844     History of Changes
Other Study ID Numbers: ANRS CO21 CODEX
Study First Received: August 9, 2011
Last Updated: July 22, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on August 25, 2014