ANRS CO24 OncoVIHAC (Onco VIH Anti Checkpoint)

Study Overview
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Brief Summary
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A Multicenter, Observational, National Cohort for HIV Infected Patients with a Cancer treated by Immune-Checkpoint Inhibitors (ICPi) for less than one month or to be treated with an ICPi such as anti-PD-1 or anti-PDL-1 or anti-CTLA4, monitored in some French hospitals . The objective of the study is to assess the safety of these new agents in HIV-infected patients. As an observatory, the number of participants planned is not predetermined: the aim is to include for 2 years any participant infected with HIV and having a cancer treated by ICPi in one of the centers that have agreed to participate. 50 participants will be recruited for Substudy OncoVIRIM during the study period (regardless of tumor type or ICPi type); 8 or 9 time points (blood samples) will be scheduled The cohort  ANRS CO24 OncoVIHAC  is declared to authorities like category 2 research . No intervention in the observatory, a collection of data will be carried out in M0, M6, M12, M18 and M24. For the physiopathological Substudy OncoVIRIM : Blood samples will be collected to constitute cell bank, plasma bank, serum bank, DNA bank in order to meet the objectives of this substudy and possibly for complementary research

Detailed Description
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Primary Objective To evaluate clinical and biological safety of the use of immune checkpoint inhibitors in HIV infected patients with cancer treated by Immune-Checkpoint Inhibitors (ICPi). Secondary objectives To evaluate evolution of HIV immunological and virological data in HIV infected patients with cancer treated by Immune-Checkpoint Inhibitors (ICPi): HIV-RNA plasma viral load Evolution of CD4+ and CD8+ T cells counts, CD4/CD8 ratio To assess the efficacy endpoint : progression-free survival, overall survival rate at 1 year and 2 years. Potential Modification of antiretroviral therapy Secondary objectives of the Physiopathological Substudy OncoVIRIM (Limited to a few clinical centers with a suitable technical tray) : To evaluate response to ICPi treatment according to RECIST criteria (solid tumor) and CHESON criteria (lymphoma) Other immunological and virological explorations on HIV : To evaluate low level HIV replication and size of the HIV reservoir To evaluate effects of ICPi on HIV-specific immune responses To show the effects of ICPi on HIV-related immune alterations such as T cell differentiation, T cell activation/exhaustion and systemic inflammation To demonstrate an effect on other viruses-specific T cells and viremia (EBV, CMV, HHV-8, HBV et HCV (if co-infected) To better understand the pathophysiology of ICPi-related immune adverse effects, particularly the development of infraclinical auto-immunity : monitoring of autoantibodies and analysis of changes in B cell antibodies repertoires To find immune biomarkers predictive for clinical response to ICPi, MHC class I and II in particular and description of any gene of interest in the context of ICPi treatment

Official Title
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A Multicenter Observational Cohort for HIV Infected Patients With a Cancer Treated by Immune-Checkpoint Inhibitors.

Conditions
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HIV Infected Patients With Cancer Treated by ICPi

Intervention / Treatment
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* Biological: Blood sample


Participation Criteria
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Eligibility Criteria
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Study Population for Cohort Inclusion criteria : Age ≥ 18 years Documented HIV-1 infection treated or untreated with antiretrovirals Cancer histologically and /or cytologically proven Person treated for less than 30 days or who should be treated with anti-PD-1 or anti-PDL-1 or anti-CTLA4 according to current recommendations Signed informed consent Exclusion Criteria - Subject participating in clinical trials CHIVA 2 (Lung Cancer- IFCT) and HANOVRE (Hodgkin's disease - LYSA) Study Population for the Physiopathological Substudy OncoVIRIM: Inclusion criteria: Participant included in the observatory Stable antiretroviral therapy (ART) with controlled HIV-RNA plasma viral load ≤ 50 copies/mL Beneficiary of a Social Security program (State Medical Aid or AME is not a Social Security program), article L1121-11 of the Public health code… Signed informed consent. Non Inclusion Criteria Brain or lung radiotherapy < 30 days Transplant organ or bone marrow transplant Corticosteroid > 10 mg per day Participant who started ICPi treatment prior to inclusion in the observatory

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Blood sample|Blood samples will be collected to constitute cell bank, plasma bank, serum bank, DNA bank in order to meet the objectives of this substudy and possibly for complementary research|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical and biological adverse events occurring with ICPi treatment during the study period |  | 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immuno-virological evolution | HIV-RNA plasma viral load copies/mL | between Month0 and Month24 | 
| Immuno-virological evolution | CD4+ and CD8+ T cells counts /mm3 and %, CD4/CD8 ratio. | between Month0 and Month 24 | 
| Disease status | Overall response rate | at Month12 and at Month24 | 
| Progression-Free survival | Progression-Free survival rate | at Month6, Month12, Month18, Month24 | 
| For Physiopathological Substudy OncoVIRIM : Objective Response Rate (OPR) | Objective response rate of patient tumor with ICPi treatment according to RECIST criteria (solid tumor) et CHESON criteria (lymphoma). The cycles of cures concerned according to the type of treatment : Nivolumab with a cure cycle length of 2 weeks : Cycle1(Week0), Cycle2 (Week2), Cycle3 (Week4), Cycle9 (Week16), Cycle15 (Week28), Cycle27 (Week52), Cycle51 (Week100) Pembrolizumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2 (Week3), Cycle3 (Week6), Cycle9 (Week24), Cycle18 (Week52), Cycle36 (Week104) Ipilimumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2(Week3), Cycle3 (Week6), Cycle4 (Week9), Month6, Month12 | At following cures cycles according to the type of treatment : Cycle1 (Week0), Cycle2 (Week2 or Week3), Cycle3 (Week4 or Week6), Cycle9 (Week16) or Cycle9 (Week24), Cycle 15(Week28), Cycle18 (Week52), Cycle27 (Week52), Cycle36 (Week104), Month6, Month12 | 
| For Physiopathological Substudy OncoVIRIM : Detailed Immunological and Virological Evolution | - Low level of HIV-RNA plasma viral load (ultrasensitive assay), HIV-DNA viral load in PBMCs (peripheral blood mononuclear cells) The cycles of cures concerned according to the type of treatment : Nivolumab with a cure cycle length of 2 weeks : Cycle1 (Week0), Cycle2 (Week2), Cycle3 (Week4), Cycle9 (Week16), Cycle 15(Week28), Cycle27 (Week52), Cycle51 (Week100), in case of treatment stopped and in case of immunological adverse event. Pembrolizumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2 (Week3), Cycle3 (Week6), Cycle9 (Week24), Cycle18 (Week52), Cycle36 (Week104) in case of treatment stopped and in case of immunological adverse event. Ipilimumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2(Week3), Cycle3 (Week6), Cycle4 (Week9), Month 6, Month 12, in case of treatment stopped and in case of immunological adverse event. | At following cures cycles according to the type of treatment : Cycle1 (Week0), Cycle2 (Week2 or Week3), Cycle3 (Week4 or Week6), Cycle9 (Week16) or Cycle9 (Week24), Cycle 15(Week28), Cycle18 (Week52), Cycle27 (Week52), Cycle36 (Week104), Month6, Month12 | 
| For Physiopathological Substudy OncoVIRIM : Detailed Immunological and Virological Evolution | - Anti-HIV Specific Immune Responses T cell (polyfunctionality and expression of immune checkpoints) The cycles of cures concerned according to the type of treatment : Nivolumab with a cure cycle length of 2 weeks : Cycle1 (Week0), Cycle2 (Week2), Cycle3 (Week4), Cycle9 (Week16), Cycle 15(Week28), Cycle27 (Week52), Cycle51 (Week100), in case of treatment stopped and in case of immunological adverse event. Pembrolizumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2 (Week3), Cycle3 (Week6), Cycle9 (Week24), Cycle18 (Week52), Cycle36 (Week104) in case of treatment stopped and in case of immunological adverse event. Ipilimumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2(Week3), Cycle3 (Week6), Cycle4 (Week9), Month 6, Month 12, in case of treatment stopped and in case of immunological adverse event. | At following cures cycles according to the type of treatment : Cycle1 (Week0), Cycle2 (Week2 or Week3), Cycle3 (Week4 or Week6), Cycle9 (Week16) or Cycle9 (Week24), Cycle 15(Week28), Cycle18 (Week52), Cycle27 (Week52), Cycle36 (Week104), Month6, Month12 | 
| For Physiopathological Substudy OncoVIRIM : Detailed Immunological and Virological Evolution | - Systemic inflammation markers and markers of T cell activation, exhaustion, and differentiation The cycles of cures concerned according to the type of treatment : Nivolumab with a cure cycle length of 2 weeks : Cycle1 (Week0), Cycle2 (Week2), Cycle3 (Week4), Cycle9 (Week16), Cycle 15(Week28), Cycle27 (Week52), Cycle51 (Week100), in case of treatment stopped and in case of immunological adverse event. Pembrolizumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2 (Week3), Cycle3 (Week6), Cycle9 (Week24), Cycle18 (Week52), Cycle36 (Week104) in case of treatment stopped and in case of immunological adverse event. Ipilimumab with a cure cycle length of 3 weeks : Cycle1 (Week0), Cycle2(Week3), Cycle3 (Week6), Cycle4 (Week9), Month 6, Month 12, in case of treatment stopped and in case of immunological adverse event. | At following cures cycles according to the type of treatment : Cycle1 (Week0), Cycle2 (Week2 or Week3), Cycle3 (Week4 or Week6), Cycle9 (Week16) or Cycle9 (Week24), Cycle 15(Week28), Cycle18 (Week52), Cycle27 (Week52), Cycle36 (Week104), Month6, Month12 | 
| For Physiopathological Substudy OncoVIRIM : | Incidence of autoimmune complications and changes in antibodies repertoires of B cell in case of immunological adverse event | between Month0 and Month24 | 
| For Physiopathological Substudy OncoVIRIM : Gene sequencing | Gene sequencing whose interest appears to be major in the responses / adverse effects of ICPi, especially MHC class I and II | Week0 |