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)

Centre Hospitalier Régional d'Orléans

Status: Enrolling

Conditions: Autophagy; Highly Active Antiretroviral Therapy; Galectins; HIV Infections

Treatments: Biological: expression of a panel

Study type: Observational

Funder types: Other

Identifiers

NCT04160455

CHRO-2019-03

Details and patient eligibility

About

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).

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

180 participants in 7 patient groups

Cohort A, group A1

Description:

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

Treatment:

Biological: expression of a panel

Cohort A, group A2

Description:

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

Treatment:

Biological: expression of a panel

Cohort B

Description:

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)

Treatment:

Biological: expression of a panel

Cohort C, group C1

Description:

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)

Treatment:

Biological: expression of a panel

Cohort C, group C2

Description:

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

Treatment:

Biological: expression of a panel

Cohort C, group C3

Description:

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

Treatment:

Biological: expression of a panel

Cohort D

Description:

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).

Treatment:

Biological: expression of a panel