NCT04805944

Gut Microbiota, PGx and INSTIs Response

Gut Microbiota, Pharmacogenetics and Integrase Strand Transfer Inhibitors Response

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 180 (actual)
• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an interventional phase IV trial enrolling HIV-infected patients treated by dolutegravir or bictegravir-based combined antiretroviral therapy, and patients with a planned shift to a dolutegravir or bictegravir-based combined antiretroviral therapy, that aims at understanding the individual response to dolutegravir and bictegravir, in terms of efficacy and toxicity.

Detailed description

The main objective of our research project is to better define the inter-individual variability in terms of clinical and biological response towards Integrase Strand Transfer Inhibitors, an important ARV drug class used in the treatment of HIV infection. We aim at identifying predictors of drug efficacy and toxicity, which are eagerly awaited by clinicians as INSTIs are now prescribed worldwide and concerns about previously unidentified side effects are emerging. The specific objectives of the project are: * To study the impact of genetic polymorphisms in selected pharmacogenes (including genes coding for biotransformation enzymes and transport proteins) on INSTIs PK parameters and biomarkers relevant for TDM, such as trough (C0) and intracellular (IC) concentrations. * To determine whether genetic polymorphisms in selected pharmacogenes might affect INSTIs efficacy, as assessed by the measurement of the viral load. * To address the important question of the pathophysiological mechanisms lying behind the two main side effects of INSTIs, namely neuropsychiatric adverse events and abnormal weight gain. * To describe how INSTIs affect the gut microbiome of treated patients, and to determine in turn how and by which pathways the gut microbiome might influence the clinical response (i.e. efficacy and toxicity) to INSTIs.

Conditions

• HIV Infections

Interventions

Type	Name	Description
DRUG	Dolutegravir	Dolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up.
DRUG	Bictegravir	Bictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
DRUG	Dolutegravir	Patient having discontinued dolutegravir will be included and samples (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
DRUG	Dolutegravir	Patients starting dolutegravir will be included and sampled both before (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) and after (blood for pharmacokinetic and metabolite profiling, stools for microbiota profiling) the start of dolutegravir
DRUG	Bictegravir	Patients starting bictegravir will be included and sampled both before (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) and after (blood for pharmacokinetic and metabolite profiling, stools for microbiota profiling) the start of bictegravir

Timeline

• Start date: 2021-03-10
• Primary completion: 2023-12-31
• Completion: 2023-12-31
• First posted: 2021-03-18
• Last updated: 2024-05-10

Locations

1 site across 1 country: Belgium