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Study of Autophagy and the Effects of GALIG Gene Products in HIV-1 Infected Patients Who Are Under Antiretroviral Therapy Since Primary-infection, Chronic Phase, or Never Treated. (ATGALIG-HIV)

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ClinicalTrials.gov Identifier: NCT04160455
Recruitment Status : Recruiting
First Posted : November 13, 2019
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Régional d'Orléans

Tracking Information
First Submitted Date November 8, 2019
First Posted Date November 13, 2019
Last Update Posted Date November 13, 2019
Actual Study Start Date November 7, 2019
Estimated Primary Completion Date November 7, 2029   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 8, 2019)
  • Quantify of a panel of genes involved in autophagy on sub-populations [ Time Frame: Quantifications will be done once for all patients (Day 0), except in cohort C where they will be repeated after they started antiretroviral therapy (at month 1, 3, 6, 12 and 24) ]
    Quantify by droplet digital PCR, the expression of a panel of 7 genes (+ GALIG) involved in autophagy on sub-populations (CD4+ and CD8+ lymphocytes and monocytes) after their sorting using magnetic bead cell then RNA extraction
  • functional test on mononuclear cell subpopulations in the autophagy function [ Time Frame: Quantifications will be done once for all patients (Day 0), except in cohort C where they will be repeated after they started antiretroviral therapy (at month 1, 3, 6, 12 and 24) ]
    Evaluate on a functional test whether the observed expression dysregulation is associated with a deregulation of the autophagic function, whether constitutive or induced.
  • Validation of the expression assays of genes involved in the autophagy function [ Time Frame: Quantifications will be done once for all patients (Day 0), except in cohort C where they will be repeated after they started antiretroviral therapy (at month 1, 3, 6, 12 and 24) ]
    Validate the expression assays of genes involved in the autophagy process and the statistical analyzes obtained on PBMCs on a validation cohort.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: November 8, 2019)
  • analyze regulatory markers on dysregulated gene promoters [ Time Frame: Tests will be done once for all patients (Day 0), except in cohort C where they will be repeated after they started antiretroviral therapy (at month 1, 3, 6, 12 and 24) ]
    To analyze regulatory markers on dysregulated gene promoters, we will analyze and compare the epigenetic marks (acetylation and methylation of histones, DNA methylation) overall and on the promoter zones of autophagy genes which present an alteration of expression.
  • quantify the reservoir of virus and ongoing viral replication [ Time Frame: Tests will be done once for all patients (Day 0), except in cohort C where they will be repeated after they started antiretroviral therapy (at month 1, 3, 6, 12 and 24) ]
    To quantify the reservoir of virus and ongoing viral replication, we will respectively evaluate the integrated viral DNA and the 2LTR circles levels.
  • analyze the phenotype of the PBMCs studied [ Time Frame: Tests will be done once for all patients (Day 0), except in cohort C where they will be repeated after they started antiretroviral therapy (at month 1, 3, 6, 12 and 24) ]
    To analyze the phenotype of the PBMCs studied, whether HIV positive or negative, we will evaluate, by analysis of surface markers in flow cytometry:
    • Distribution of CD3+CD4+, CD3+CD8+, NK, B, NK-T and monocyte populations
    • Activation (HLA-DR and CD38 on T cells; HLA-DR, CD11b and CD16 on monocytes)
    • Senescence (CD57+ on CD8+ T cells, CD7- on CD4+ T cells)
    • Exhaustion (PD1 / CD279)
    • Distribution of memories, naive and effector CD4+ and CD8+ lymphocytes (CD45RA and CCR7 / CD197)
    • Proliferative capacity of PBMCs
  • Evaluation of the level of inflammation [ Time Frame: Tests will be done once for all patients (Day 0), except in cohort C where they will be repeated after they started antiretroviral therapy (at month 1, 3, 6, 12 and 24) ]
    To assess the level of inflammation, we will dose the inflammatory cytokines present in the patients' serum and controls.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Study of Autophagy and the Effects of GALIG Gene Products in HIV-1 Infected Patients Who Are Under Antiretroviral Therapy Since Primary-infection, Chronic Phase, or Never Treated.
Official Title Study of Autophagy and the Effects of GALIG Gene Products in HIV-1 Infected Patients Who Are Under Antiretroviral Therapy Since Primary-infection, Chronic Phase, or Never Treated.
Brief Summary

Little is known about autophagy during HIV infection. Recently, two different teams reported important dysfunctions of autophagy in HIV-infected patients despite sustained suppressive antiretroviral therapy. As altered autophagy is strongly linked to cellular senescence and chronic inflammation, two hallmarks of HIV-infected patients despite long-term suppressive antiretroviral therapy, it is important to improve our knowledge in the area.

Our main objective is to determine whether all or part of mononuclear cell subpopulations (CD4+ and CD8+ T lymphocytes, and monocytes) exhibit a defect in autophagy function in a cohort of HIV-infected patients who are virologically-controlled (plasma HIV RNA <50 copies / ml) either spontaneously (i.e. HIV controllers or post-treatment controllers) or after they started antiretroviral therapy at different time points (i.e. at the acute or chronic phases), as compared with a control group (i.e. uninfected healthy blood donors).

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood
Sampling Method Non-Probability Sample
Study Population All HIV-1-infected adults (not co-infected with HIV-2), followed at the Infectious Diseases Department of Orleans' Regional Hospital and meeting the inclusion criteria, will be offered to participate in the study.
Condition
  • Autophagy
  • Galectins
  • HIV Infections
  • Highly Active Antiretroviral Therapy
Intervention Biological: expression of a panel
Quantify, by droplet digital PCR, the expression of a panel of 7 genes (+ GALIG) involved in autophagy2 on sub-populations (CD4+ and CD8+ lymphocytes and monocytes) after their sorting using magnetic bead cell then RNA extraction Evaluate, on a functional test (as previously described1), whether the observed expression dysregulation is associated with a deregulation of the autophagic function, whether constitutive or induced.
Study Groups/Cohorts
  • Cohort A, group A1
    40 patients on suppressive antiretroviral therapy (HIV RNA <50 copies / ml for at least 4 years) initiated during the chronic phase : CD4 count less than 500 cells / ml at the time of inclusion in the study
    Intervention: Biological: expression of a panel
  • Cohort A, group A2
    40 patients on suppressive antiretroviral therapy (HIV RNA <50 copies / ml for at least 4 years) initiated during the chronic phase: CD4 count above 500 cells / ml at the time of inclusion in the study
    Intervention: Biological: expression of a panel
  • Cohort B
    20 patients on suppressive antiretroviral therapy (HIV RNA <50 copies / ml for at least 4 years) initiated since the primary-infection (within 4 months after acute infection)
    Intervention: Biological: expression of a panel
  • Cohort C, group C1
    20 patients with detectable HIV RNA, naïve of antiretroviral, but who have an indication to start antiretroviral therapy: HIV diagnosis made during primary infection (within 4 months of infection)
    Intervention: Biological: expression of a panel
  • Cohort C, group C2
    20 patients with detectable HIV RNA, naïve of antiretroviral, but who have an indication to start antiretroviral therapy: HIV diagnosis made during the chronic phase (more than 1 year after contamination), with CD4 count above 200 cells/ml at the time of inclusion in the study
    Intervention: Biological: expression of a panel
  • Cohort C, group C3
    20 patients with detectable HIV RNA, naïve of antiretroviral, but who have an indication to start antiretroviral therapy: HIV diagnosis made during the chronic phase (more than 1 year after contamination), with CD4 count less than 200 cells/ml at the time of inclusion in the study
    Intervention: Biological: expression of a panel
  • Cohort D
    20 patients who have undetectable plasma HIV RNA (HIV RNA <50 copies / ml ) without antiretroviral therapy, either spontaneously (HIV controllers or elite controllers) or after treatment interruption (post-treatment controllers).
    Intervention: Biological: expression of a panel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 8, 2019)
180
Original Estimated Enrollment Same as current
Estimated Study Completion Date November 7, 2029
Estimated Primary Completion Date November 7, 2029   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

General criteria:

  • Age >=18 years
  • Man or woman
  • Infected with HIV-1 (and not co-infected with HIV-2)
  • Followed at Orleans' Regional Hospital
  • Patient belonging to one of the predefined cohorts/groups (see below)
  • Patient having provided a written consent

Specific profiles of HIV-infected patients for the ATGALIG-HIV study:

Cohort A: patients on suppressive antiretroviral therapy (HIV RNA <50 copies / ml for at least 4 years) initiated during the chronic phase, divided into 2 groups according to the following criteria:

  • group A1: CD4 count less than 500 cells / ml at the time of inclusion in the study
  • group A2: CD4 count above 500 cells / ml at the time of inclusion in the study Cohort B: patients on suppressive antiretroviral therapy (HIV RNA <50 copies / ml for at least 4 years) initiated since the primary-infection (within 4 months after acute infection)

Cohort C: patients with detectable HIV RNA, naïve of antiretroviral, but who have an indication to start antiretroviral therapy, divided into the following 3 groups:

  • group C1: HIV diagnosis made during primary infection (within 4 months of infection)
  • group C2: HIV diagnosis made during the chronic phase (more than 1 year after contamination), with CD4 count above 200 cells/ml at the time of inclusion in the study
  • group C3: HIV diagnosis made during the chronic phase (more than 1 year after contamination), with CD4 count less than 200 cells/ml at the time of inclusion in the study Cohort D: patients who have undetectable plasma HIV RNA (HIV RNA <50 copies / ml ) without antiretroviral therapy, either spontaneously (HIV controllers or elite controllers) or after treatment interruption (post-treatment controllers)

Exclusion Criteria:

  • Patient unable, according to the investigator, to meet the requirements of the protocol
  • Pregnant or lactating woman
  • Patient with a history of inflammatory bowel disease, malignancy, intestinal ischemia, malabsorption or other gastrointestinal dysfunction that, in the judgment of the investigator, could interfere with the interpretation of the results.
  • Presence of coagulation abnormality or unexplained bleeding history
  • Treatment with oral or injectable anticoagulant (curative or preventive)
  • Patient covered by Article L.1121-5 to L.1121-8 and L.1122-1-2 of the French Public Health Code (including minors and protected adults)
  • Patient under guardianship or curatorship
  • Patient who uncovered by French health insurance Patient participating in another clinical trial, evaluating a treatment
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Aurélie DESPUJOLS 0238744071 ext +33 aurelie.despujols@chr-orleans.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT04160455
Other Study ID Numbers CHRO-2019-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Centre Hospitalier Régional d'Orléans
Study Sponsor Centre Hospitalier Régional d'Orléans
Collaborators Not Provided
Investigators
Principal Investigator: Laurent HOCQUELOUX, Dr CHR d'orléans
PRS Account Centre Hospitalier Régional d'Orléans
Verification Date November 2019