Gut Microbiota, PGx and INSTIs Response

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Status: Completed

Conditions: HIV Infections

Treatments: Drug: Bictegravir; Drug: Dolutegravir

Study type: Observational

Funder types: Other

Identifiers

NCT04805944

INSTI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion will be proposed to:

• HIV infected adult patient regularly followed at Centre de reference HIV of CUSL and currently treated by 50mg OD of DTG (n=80) or 50mg OD of BIC (n=30).
• Virally controlled immunologically functional HIV infected adult patient regularly followed at Centre de reference HIV of CUSL and shifting from another ARV class to a treatment containing 50mg OD of DTG (n=20) or 50mg OD of BIC (n=20).
• HIV infected adult patient retrospectively identified as having stopped standard dosage of DTG (ie. 50mg OD) due to NPAE (insomnia, depression, anxiety) (n=50). Identification will be based on the interrogation of our prospective clinical database.

Exclusion Criteria:

• Pregnancy at the time of inclusion or expected pregnancy within 12 months, for patients treated by DTG or BIC during the study
• Liver failure (Child-Pugh A, B or C)

Trial design

180 participants in 5 patient groups

DTG treated (A)

Description:

80 HIV-infected adults treated with dolutegravir (as a component of their usual provider-prescribed antiretroviral regimen)

Treatment:

Drug: Dolutegravir

Drug: Dolutegravir

Drug: Dolutegravir

BIC treated (B)

Description:

30 HIV-infected adults treated with bictegravir (as a component of their usual provider-prescribed antiretroviral regimen)

Treatment:

Drug: Bictegravir

Drug: Bictegravir

DTG discontinued due to neuropsychiatric adverse event (C)

Description:

50 HIV-infected adults having stopped dolutegravir due to neuropsychiatric adverse effects (insomnia, depression, anxiety)

Treatment:

Drug: Dolutegravir

Drug: Dolutegravir

Drug: Dolutegravir

Shifting to DTG (D)

Description:

20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing dolutegravir

Treatment:

Drug: Dolutegravir

Drug: Dolutegravir

Drug: Dolutegravir

Shifting to BIC (E)

Description:

20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing bictegravir

Treatment:

Drug: Bictegravir

Drug: Bictegravir