Overview
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
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