HIV and Changes in the Gut Microbiome After Changes in Antiretroviral Therapy (ART)

A Prospective Observational Study of the Impact on the Gut Microbiome in HIV-infected Individuals in Manchester, UK, When Switching From One Class of Antiretroviral Drugs or Delivery Method to Another Class or Delivery Method.

This is a study that aims to contribute to the understanding of how antiretroviral therapy effects the gut microbiome which, if known, could inform decisions about drug choices at an individual level.

The gut health is extremely important for all aspects of a persons wellbeing both at the level of the body and the brain. In recent years there has been much interest and better understanding of the role of the bacteria, viruses and other microorganisms that live in the human gut (the gut microbiome). It is known that disturbing the balance between the different species of bacteria in the gut can have consequences including diarrhoea, inflammatory and autoimmune conditions and has also been linked to obesity.

There are big differences in the gut microbiome composition seen in people with untreated HIV infection compared with non-infected individuals. This disrupted balance does not seem to be restored when starting on antiretroviral therapy. Different classes of antiretrovirals seem to have different effects but this has been hard to establish because studies aiming to look at this has been large population studies where it can be hard to tease out cause and effect.

In this study the investigators are instead aiming to compare an individual with themselves by comparing the bacterial gut microbiome before the person switches from one class of antiretroviral treatment to another or switches the delivery method of that drug, with the bacterial gut microbiome 3-8 weeks after the switch.

The investigators hope that if this can be understood the effects different classes and delivery methods of antiretroviral have on an individual's gut microbiome, can be taken into account when deciding on the best HIV therapy for a person. In the long term, this would lessen the negative effects of being on a life-long treatment.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Gabriella LA Lindergard, PhD; Phone Number: +447855212958; Email: gabriella.lindergard@manchester.ac.uk

Study Locations

• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Recruiting
      • Manchester University NHS Foundation Trust
      • Contact: Elizabeth Mainwaring; Phone Number: +44 161 276 3340; Email: R&D.applications@mft.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HIV infected individuals on stable antiretroviral treatment.

Description

Inclusion Criteria:

• Aged ≥18 years.
• Willing to undergo stool sample collection on two occasions.
• Able to give written, informed consent.
• Have evidence of HIV infection
• Have been on stable antiretroviral treatment for the previous ≥12months.
• Planning to switch ART regimen from one class of drugs or delivery method to another.

Exclusion Criteria:

• HIV viral load >50 copies/ml blood

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ART switch group; These are individuals who complete a planned switch of ART regimen from one class of drugs or delivery method to another.
Control group; This group continue on their stable ART regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure changes in diversity and abundance of bacterial species in stool sample collected before and after a change of ART.	The number of different bacterial species and the abundance of these species will be measured by shallow shotgun sequencing before and after the change in antiretroviral treatment.	3-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To link level of bacterial diversity with different ART regiments.	To measure the level of change in the number and the abundance of bacterial species after a change of antiretroviral treatment.	3-8 weeks

Collaborators and Investigators

• Sponsor: University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: October 20, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 25, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: HIV; Gut microbiome; Antiretroviral drugs
• 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: 333914

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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