Clinical trial NCT04160455: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autophagy
Galectins
HIV Infections
Highly Active Antiretroviral Therapy
Keywords: Antiretroviral therapy
basal autophagy
GALIG gene
HIV
apoptosis
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
First posted: 2019-11-13
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

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).


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

Primary outcomes:
measure: Quantify of a panel of genes involved in autophagy on sub-populations
timeFrame: 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)
measure: functional test on mononuclear cell subpopulations in the autophagy function
timeFrame: 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)
measure: Validation of the expression assays of genes involved in the autophagy function
timeFrame: 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:
measure: analyze regulatory markers on dysregulated gene promoters
timeFrame: 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)
measure: quantify the reservoir of virus and ongoing viral replication
timeFrame: 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)
measure: analyze the phenotype of the PBMCs studied
timeFrame: 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)
measure: Evaluation of the level of inflammation
timeFrame: 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)
Other outcomes:
Locations:
city: Orléans
country: France
facility: CHR d'Orleans
Study officials:
affiliation: CHR d'orléans
name: Laurent HOCQUELOUX, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.