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

September 24, 2026 updated by: Hospices Civils de Lyon

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: COHORT
  • Time Perspectives: PROSPECTIVE

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identifying immune profiles associated with better control of this reservoir.
Time Frame: Day 1

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Florence ADER, M.D.,PhD., Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 12, 2027

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

September 24, 2026

First Submitted That Met QC Criteria

September 24, 2026

First Posted (Actual)

September 30, 2026

Study Record Updates

Last Update Posted (Actual)

September 30, 2026

Last Update Submitted That Met QC Criteria

September 24, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL26_0720
  • 2026-A02069-42 (Other Identifier: ID-RCB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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