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.

NCT04160455 | Recruiting

• 1 other identifier: CHRO-2019-03
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

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).

Conditions

Galectins; Highly Active Antiretroviral Therapy; Autophagy; HIV Infections

Keywords

Antiretroviral therapy; basal autophagy; GALIG gene; HIV; apoptosis

Outcome Measures

Primary Outcomes (3)

• Quantify of a panel of genes involved in autophagy on sub-populations

  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

  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)

• functional test on mononuclear cell subpopulations in the autophagy function

  Evaluate on a functional test whether the observed expression dysregulation is associated with a deregulation of the autophagic function, whether constitutive or induced.

  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)

• Validation of the expression assays of genes involved in the autophagy function

  Validate the expression assays of genes involved in the autophagy process and the statistical analyzes obtained on PBMCs on a validation cohort.

  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)

Secondary Outcomes (4)

• analyze regulatory markers on dysregulated gene promoters

  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)

• quantify the reservoir of virus and ongoing viral replication

  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)

• analyze the phenotype of the PBMCs studied

  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)

• Evaluation of the level of inflammation

  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)

Study Arms (7)

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

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

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)

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)

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

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

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).

Biological: expression of a panel

Interventions

expression of a panel BIOLOGICAL

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.

Cohort A, group A1; Cohort A, group A2; Cohort B; Cohort C, group C1; Cohort C, group C2; Cohort C, group C3; Cohort D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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:
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Régional d'Orléans: lead

Study Sites (1)

CHU Orleans

Orléans, 45067, France

RECRUITING

Related Publications (4)

• Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013 Nov 2;382(9903):1525-33. doi: 10.1016/S0140-6736(13)61809-7. Epub 2013 Oct 23.

  PMID: 24152939 BACKGROUND

• Ipp H, Zemlin A. The paradox of the immune response in HIV infection: when inflammation becomes harmful. Clin Chim Acta. 2013 Feb 1;416:96-9. doi: 10.1016/j.cca.2012.11.025. Epub 2012 Dec 7.

  PMID: 23228847 BACKGROUND

• Serrano A, El Haddad S, Moal F, Prazuck T, Legac E, Robin C, Brule F, Charpentier S, Normand T, Legrand A, Hocqueloux L, Mollet L. Dysregulation of apoptosis and autophagy gene expression in peripheral blood mononuclear cells of efficiently treated HIV-infected patients. AIDS. 2018 Jul 31;32(12):1579-1587. doi: 10.1097/QAD.0000000000001851.

  PMID: 29734217 BACKGROUND

• Gomez-Mora E, Robert-Hebmann V, Garcia E, Massanella M, Clotet B, Cabrera C, Blanco J, Biard-Piechaczyk M. Brief Report: Impaired CD4 T-Cell Response to Autophagy in Treated HIV-1-Infected Individuals. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):201-205. doi: 10.1097/QAI.0000000000001201.

  PMID: 27787338 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Laurent HOCQUELOUX, Dr

  CHR d'orléans

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aurélie DESPUJOLS

CONTACT

0238744071; aurelie.despujols@chr-orleans.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 13, 2019
• Study Start: November 7, 2019
• Primary Completion (Estimated): November 7, 2029
• Study Completion (Estimated): November 7, 2039
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

FR (1)