Evolution of HIV Reservoir, Inflammation and Microbiota Footprint of PLWH Switching to Long-acting Injectable Treatment Compared to Patients on Oral Dual or Triple Anti-integrase-based Therapy (LAMIVIH)

Evolution of HIV Reservoir, Inflammation and Microbiota Footprint of PLWH Switching to Long-acting Injectable Treatment Compared to Patients on Oral Dual or Triple Anti-integrase-based Therapy: a Prospective Longitudinal Comparative Study

In the last 40 years of HIV history, we have managed to attain most of our therapeutic objectives, namely virological suppression of most patients and sufficient immune reconstitution. Still, immune activation and inflammation persist and even if they decrease on ART (AntiRetroviral Treatment), they do not disappear and may be associated to multiple non-AIDS related comorbidities.

In this population structural and functional modifications of GALT (Gut Associated Lymphoïd Tissue) are observed early after HIV infection and persist despite virological suppression on ART. Moreover, imbalance of the gut microbiota which is called dysbiosis may participate in persistent activation and therefore enhancement of residual HIV viral replication.

GALT modifications are associated with microbial translocation that is also correlated with immune activation and dysbiosis.

Up to now, there is no evidence of a differential impact on inflammation, immune activation or cellular reservoirs of different ART regimens. Long-Acting (LA) regimens could theoretically display better inflammatory profile, since they have a better tissue distribution and could act more efficiently on HIV reservoirs. On the other hand, LA's direct administration shunting the gut passage could also contribute to less gut dysbiosis.

The objective of our study is to assess impact on plasma biomarkers, cell-surface biomarkers, intestinal microbiota and cellular reservoirs of a switch from an oral dual or triple anti-integrase-based therapy ART regimen including an anti-integrase compared to a Long-Acting (LA) injectable treatment.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Other: Stool sampling; Other: Blood plasma collection

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Myriam BENNANI; Phone Number: 0413428351; Email: m.bennani@hopital-europeen.fr

Study Locations

• France
  • Marseille, France, 13003
    • Recruiting
    • Hôpital Européen Marseille
    • Contact: Myriam BENNANI
    • Principal Investigator: Christina PSOMAS, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

People Living with HIV (PLWH)

Description

Inclusion Criteria:

• PLWH at a the stable phase of their disease (absence of disease outbreak and absence of treatment modification in the 3 months preceding inclusion),
• Subject with ongoing HIV follow-up on an outpatient basis (outpatient or day hospital consultation) in the participating center, and having virological suppression at the threshold of 50 copies / mL for at least 1 year (blips < 200 copies / mL tolerated during this period)
• CD4 + T cell nadir> 200 / mm3
• Having given free and informed written consent
• Being affiliated with or benefiting from a social security scheme.

Exclusion Criteria:

• Persons treated with antibiotics, probiotics, prebiotics or any other treatment that may disrupt the gut microbiota within two month before stool sampling.
• Subject only coming for full impatient follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients switching towards a long-aging injectable treatment	Other: Stool sampling; Stool samples will be collected from participants at baseline and W52; Other: Blood plasma collection; Blood plasma collection to assess persistent inflammation, immune activation and HIV reservoir at baseline,W24,W52
Patients maintaining oral ART 2-drug regimens	Other: Stool sampling; Stool samples will be collected from participants at baseline and W52; Other: Blood plasma collection; Blood plasma collection to assess persistent inflammation, immune activation and HIV reservoir at baseline,W24,W52
Patients maintaining oral ART 3 drug regimens	Other: Stool sampling; Stool samples will be collected from participants at baseline and W52; Other: Blood plasma collection; Blood plasma collection to assess persistent inflammation, immune activation and HIV reservoir at baseline,W24,W52

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Variation of the HIV cellular reservoirs at W52 of two switch comparatively to baseline among the 3 groups of PLWH	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Variation of the Shannon index between 0 and 1 year in the different groups of PLWH compared to baseline	12 months
Variation of the immune profile in participants with an LA-based regimen compared to participants with an oral therapy at W24 and W52	12 months
Correlation between the immune profile and the Shannon index at W52 among the different groups of PLWH	12 months
Correlation between the immune profile and the HIV-reservoirs at W52 among the different groups of PLWH	12 months

Collaborators and Investigators

• Sponsor: Hôpital Européen Marseille

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections
• Other Study ID Numbers: 21-40

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No