Clinical trial NCT04805944: Gut Microbiota, PGx and INSTIs Response
Official title: Gut Microbiota, Pharmacogenetics and Integrase Strand Transfer Inhibitors Response
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: integrase strand transfer inhibitors
hiv
dolutegravir
bictegravir
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2021-03-18
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects will be recruited among regularly HIV-infected patients regularly followed at the Centre de Prise en charge VIH of Cliniques universitaires Saint-Luc - UCLouvain

Brief 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.

Eligibility 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)

Primary outcomes:
measure: Dolutegravir and bictegravir through concentration
timeFrame: 24 hours post last dose
measure: Dolutegravir and bictegravir intracellular concentration
timeFrame: 24 hours post last dose
measure: Viral replication
timeFrame: At least 3 months after the initiation of DTG/BIC
measure: Microbiota profile under treatment
timeFrame: At least 6 months after the initiation of DTG/BIC
measure: Change of microbiota profile
timeFrame: Baseline and at 6 months
measure: Change in weight
timeFrame: Through study completion, an average of 1 year
measure: Psychometric evaluation (Symptom-checklist-90-R)
timeFrame: At least 3 months after the initiation of DTG/BIC
measure: Change of psychometric evaluation (Symptom-checklist-90-R)
timeFrame: Baseline and at 6 months
measure: Psychometric evaluation (Pittsburgh Sleep Quality Index)
timeFrame: At least 3 months after the initiation of DTG/BIC
measure: Change of psychometric evaluation (Pittsburgh Sleep Quality Index)
timeFrame: Baseline and at 6 months
measure: Psychometric evaluation (Pichot's fatigue scale)
timeFrame: At least 3 months after the initiation of DTG/BIC
measure: Change of psychometric evaluation (Pichot's fatigue scale)
timeFrame: Baseline and at 6 months
measure: Psychometric evaluation (Hospital Anxiety and Depression Scale)
timeFrame: At least 3 months after the initiation of DTG/BIC
measure: Change of psychometric evaluation (Hospital Anxiety and Depression Scale)
timeFrame: Baseline and at 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
Study officials:
affiliation: Cliniques universitaires Saint-Luc; UCLouvain/IREC/LTAP
name: Leïla Belkhir, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: