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.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Quantify of a panel of genes involved in autophagy on sub-populations
研究概览
简要总结
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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
干预措施: expression of a panel (Biological)
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
干预措施: expression of a panel (Biological)
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)
干预措施: expression of a panel (Biological)
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)
干预措施: expression of a panel (Biological)
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
干预措施: expression of a panel (Biological)
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
干预措施: expression of a panel (Biological)
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).
干预措施: expression of a panel (Biological)
结局指标
主要结局
Quantify of a panel of genes involved in autophagy on sub-populations
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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 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))
- 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))
- 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))