Innate-like and NK Signatures in Chronic-Treated HIV Infection INSTINCT-HIV

NCT07849933 | Not Yet Recruiting

• 2 other identifiers: 69HCL26_07202026-A02069-42
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Infection with the human immunodeficiency virus (HIV) is a chronic condition requiring lifelong antiretroviral therapy (ART). Despite prolonged virological control under suppressive ART, HIV persists in the form of a stable viral reservoir known as the 'integrated' reservoir, mainly localised in CD4+ memory T cells, which constitutes the obstacle to a functional or sterilising cure of the infection. The immunological mechanisms involved in the control, stability or gradual depletion of this reservoir are still not fully understood. Among the cellular populations of the innate immune system, Natural Killer (NK) cells play an important role in the trajectory of the reservoir by having the ability to eliminate HIV-infected cells. However, several studies have shown that these NK cells exhibit variable capabilities in eliminating such cells, suggesting that inter-individual heterogeneity in innate immune responses may contribute to the observed differences in the size and persistence of the viral reservoir in people living with HIV (PLHIV) on long-term suppressive ART. Functionally, interactions between NK cell receptors and class I HLA molecules (HLA I) strongly modulate the education, repertoire and effector functions of NK cells, indicating that the immunogenetics of the host's HLA I alleles is therefore a major determinant of this variability. Certain receptor/HLA I combinations, notably receptors known as KIRs, have been associated with differences in the progression of HIV infection and immunovirological control. Consequently, their role in the dynamics of the viral reservoir during prolonged suppressive ART needs to be explored. Finally, biological sex significantly influences anti-HIV immune responses, with females showing a favourable response. Whilst sex differences in NK cell function and immune activation have been described, the impact of biological sex on the dynamics of the HIV reservoir under prolonged suppressive ART remains largely unknown and requires further investigation

Conditions

Human Immunodeficiency Virus Infection (HIV)

Keywords

Human Immunodeficiency Virus Infection (HIV); Antiretroviral therapy; Viral reservoir; NK cells

Outcome Measures

Primary Outcomes (1)

• Identifying immune profiles associated with better control of this reservoir.

  The primary endpoint is a composite measure combining the phenotypic and functional characterisation of NK cells and related cells of the innate immune system, and the number of mononuclear cells infected with HIV provirus (reservoir).

  Day 1

Study Arms (1)

People living with HIV

Adult patients living with HIV who have been receiving prolonged, continuous, suppressive antiviral treatment for at least five full years.

Biological: Blood test

Interventions

Blood test BIOLOGICAL

A 50 ml venous blood sample is taken upon the participant's enrolment

People living with HIV

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The target population consists of adults aged 18 years or over living with HIV who are being monitored by the Department of Infectious and Tropical Diseases at the Hospices Civils de Lyon and who have been receiving prolonged, continuous, suppressive antiviral treatment for at least five full years. Participants must meet the following criteria: * a plasma viral load that has been consistently undetectable since the start of ART and for more than 5 years; * must not have experienced, since the start of antiviral treatment, more than two isolated episodes of virological rebound ('blips') ≥ 100 copies/mL, measured in a peripheral blood sample taken during a routine consultation.

You may qualify if:

• Be aged 18 or over;
• Be living with HIV-1 infection;
• Be under the care of the Department of Infectious and Tropical Diseases at the Lyon university Hopsital (Hospices Civils de Lyon);
• Have been receiving continuous ART for at least 5 full years;
• Have a consistently undetectable plasma HIV viral load whilst on ART;
• Have experienced no more than two isolated episodes of virological rebound ('blips') ≥ 100 copies/mL;
• Have usable biological samples for the planned analyses and/or agree to the collection of samples required for the research;
• Have received written and verbal information about the research;
• Have signed the written consent form prior to any research-specific procedures.

You may not qualify if:

• Patients who have taken part in an interventional therapeutic trial specifically targeting an HIV cure strategy likely to have a lasting effect on the immunological or virological parameters under investigation;
• Patients who have experienced more than two episodes of virological rebound ≥ 100 copies/mL whilst on ART;
• Pregnant women, women in labour or breastfeeding women;
• Persons deprived of their liberty by judicial or administrative order;
• Persons subject to a legal protection order;
• Adults subject to a legal protection measure (guardianship, curatorship);
• Persons admitted to a health or social care facility for purposes other than research;
• Persons receiving psychiatric care;
• Persons who have expressed their objection to participating in the research or to the use of their data and biological samples.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Biospecimen

Retention: SAMPLES WITH DNA

50 ml of venous blood will be collected in 10 EDTA or citrate tubes at the time of the patient's enrolment

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Florence ADER, M.D.,PhD.

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Florence ADER, M.D.,PhD.

CONTACT

472071107; florence.ader@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2026
• First Posted: September 30, 2026
• Study Start (Estimated): January 12, 2027
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 30, 2026

Record last verified: 2026-09