The principal objective is to define and compare the viral reservoir, mucosal immune responses and the microbiota of different HIV infection stages; viremic, aviremic (under treatment), natural elite controllers; The secondary objective is to compare the mucosal immune response and microbiota of HIV patients with the healthy control population of Milieu Interieur;

Although antiretroviral therapy (ART) efficiently suppresses viral replication HIV persists in CD4+ T cells in a form that is neither targeted by the immune system nor by ART, the complete eradication of replication competent HIV or the establishment of a long term remission state in infected individuals represents an outstanding challenge.

The persistence of reservoirs has been mainly linked to the survival and clonal expansion of pools of long lived infected memory CD4+ T cells and to low level viral replication in tissues where ART penetration may be incomplete. One such tissue may be mucosal surfaces which are challenging to study in human populations.

As part of the Milieu Interieur project, coordinated by Institut Pasteur, investigators have developed and validated a standardized approach for sampling the nasal mucosa. From this simple sampling procedure it is possible to analyze both the local mucosal host immune response at the proteomic and metabolomic level, and also the mucosal microbial flora.

As part of Milieu Interieur investigators have defined these diverse phenotypes for a subset of donors and are currently extending the analysis to the 1,000 healthy donors cohort that will give reference range values for the nasal mucosa.

Investigators wish to compare with relevant patient groups, in particular HIV infected individuals to see how infection, treatment, and natural host control may differentially impact the mucosal immune response and viral reservoir

Inclusion Criteria:

• Chronic HIV-1 infected subjects followed in Department of Internal Medicine and Clinical Immunology in Bicetre Hospital

• Healthy male or female aged between 20 and 69 (included) years

• Whatever the clinical status and the lymphocytes T CD4+

• Patients treatment-naive or under ARV treatment whatever the molecules

• 3 groups of patients, according to their HIV1 viral loads

  • Virémic : viral load > 500 copies/mL, treatment-naive or treated (failing) regardless of the cause of persistent viremic
  • No Viremic : < 50 copies/ml under treatment at least from 12 months
  • Spontaneous Controllers from the Codex Cohort (Controllers cohort from ANRS) or not with the following inclusion criteria Chronic HIV-1 infected subjects since 5 years, asymptomatic With 5 last viral loads < 400 copies /mL Whatever the lymphocytes T CD4 rates Naive of treatment except transient treatment for prevention of mother-to-child transmission

• Subject considered to be free on the day of study of an acute condition or infection that may interfere with the results of the study, based on the clinical examination performed by the investigator

• Caucasian and Sub Saharan patients -18,5 ≤ BMI ≤ 32 kg/m²

• Subjects who, according to the investigator, can and will comply with the requirements of the protocol and are available for the scheduled visit at the investigational site. Ability to give their informed consent in writing

• Affiliated to the French social security or assimilated regimens

Exclusion Criteria:

Participation in another clinical study in the last 3 months

• Travel in (sub-) tropical countries within the last 3 months

• Pregnant women

• Infectious diseases:

  • Acute opportunistic or not, current or past infection, within the last 3 months as determined by the PI
  • Ear temperature ≥ 38.4 ° C on the day of inclusion
  • Subject currently receiving or having received in the last 3 months antibiotics or nasal, intestinal or respiratory antiseptics

• Severe/chronic/recurrent pathological conditions, among them:

  • Past or present diagnosed cancer, lymphoma, leukemia to the exception of: Persons with a history of cancer who are disease-free without treatment for 5 years or more
  • Women who are disease free for 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen
  • Cutaneous or cervical basal cell carcinoma
  • Personal history of organ transplant
  • Congenital or acquired immune deficiency (any confirmed or suspected immunosuppressive or immunodeficient condition, including history of HIV infection)
  • Personal history of auto-immune diseases requiring or having previously required treatment (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sarcoidosis, Ankylosing Spondylitis, Autoimmune Hemolytic Anemia, Autoimmune Thrombocytopenic Purpura, Crohn's Disease, Psoriasis, Scleroderma, Wegener's Granulomatosis,Type I Diabetes, Thyroiditis,….)
  • Splenectomy
  • Acute or chronic, clinically significant, as determined by the investigator, pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory
  • Chronic renal impairment as defined by Renal Insufficiency: GFR<60 mL/min/1.73 m² (National Kidney Foundation (2002)
  • History of clinically significant, as determined by the investigator, neurological disorder or seizures
  • Any physical activity within 8 hours before the visit
  • Any significant disorder of coagulation or treatment with warfarin derivatives (AVK or ACO)or heparin or antiplatelet medications within 2 months preceding inclusion

• Severe acute/chronic allergy

  • Severe Asthma defined as asthma requiring a combination of two or more controller therapies (e.g. medium or high dose inhaled glucocorticosteroid and long-acting inhaled beta-2 agonist) or requiring oral glucocorticosteroids (GINA),
  • Severe insect bite allergy with history of giant urticaria, Quincke edema or anaphylactic shock

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to the inclusion. For corticosteroids, this will mean a dose equivalent to 20 mg/day of prednisone or equivalent for > 2 weeks (inhaled and topical steroids allowed)

• Chronic administration of NSAIDs, including aspirin: prolonged intake (> 2 weeks) within 6 months before study

• Receipt of blood products or immunoglobulins within 3 months prior the inclusion or planning to receive blood products or immunoglobulins during the study

• Hemoglobin measurement less than 10.0 g/dL for women and less than 11.5 g/dL for men

• Platelet count less than 120.000/mm3

• ALAT and/or ASAT > 3 times the upper limit of the norm (ULN)

• Receipt of any vaccination 3 months before the inclusion

• Alcohol abuse (more than 50 g of pure ethanol per day: for example, more than 4 x 150 mL glasses of wine, more than 4 x 250 mL glasses of beer, more than 4 x 40 mL glasses of high alcohol content drinks

• Illicit drug use or substance abuse within 3 months prior to inclusion

110 patients followed in Department of Internal Medicine and Clinical Immunology Bicetre Hospital APHP Chronic HIV-1 infected subjects

• 50 Viremic subjects : plasma HIV RNA > 500 copies/mL, treatment-naive or treated (failing) regardless of the cause of persistent viremia
• 50 Treated Aviremic subjects : < 50 copies/mL under treatment for at least 12 months
• 10 Spontaneous Controllers from the ANRS CO21 CODEX Cohort or not (5 last viral loads < 400 copies /ml)

Data will be entered electronically via a web browser in Electronic Case Report Form Data will be analysed by Pasteur Institute of Paris with the biological results

At the end of the study

The persons responsible for the quality control of clinical studies (the French Public Health Code) will take all necessary precautions to ensure the confidentiality of information relating to the research, the participants and in particular their identity and the results obtained. These persons, as well as the investigators themselves, are bound by professional secrecy. During and after the research, all data collected about the participants and sent to the Pasteur Institute of Paris by the investigators will be anonymized. Under no circumstances will the names and addresses of the participants be shown. The sponsor will ensure that each participant has agreed in writing for any personal information about him or her which is strictly necessary for the quality control of the study to be accessed Identification of the person responsible and the location for data processing. Statistical analysis will be performed by scientist and IPP bio-informatician within the research units involved.