Gut Microbiota, PGx and INSTIs Response
- Registration Number
- NCT04805944
- Lead Sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 180
Not provided
- 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)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Shifting to BIC (E) Bictegravir 20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing bictegravir DTG treated (A) Dolutegravir 80 HIV-infected adults treated with dolutegravir (as a component of their usual provider-prescribed antiretroviral regimen) BIC treated (B) Bictegravir 30 HIV-infected adults treated with bictegravir (as a component of their usual provider-prescribed antiretroviral regimen) Shifting to DTG (D) Dolutegravir 20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing dolutegravir DTG discontinued due to neuropsychiatric adverse event (C) Dolutegravir 50 HIV-infected adults having stopped dolutegravir due to neuropsychiatric adverse effects (insomnia, depression, anxiety)
- Primary Outcome Measures
Name Time Method Change in weight Through study completion, an average of 1 year Overall weight change between treatment initiation through study completion
Change of psychometric evaluation (Hospital Anxiety and Depression Scale) Baseline and at 6 months Change from baseline Hospital Anxiety and Depression Scale at 6 month after treatment initiation, for groups D and E.
Hospital Anxiety and Depression Scale scores answers between 0 and 21 for its two compoinents, anxiety and depression. A higher score means a worse outcome.Change of microbiota profile Baseline and at 6 months Change from baseline microbiota profile at 6 month after treatment initiation, for groups D and E
Psychometric evaluation (Symptom-checklist-90-R) At least 3 months after the initiation of DTG/BIC Psychometric evaluation through Symptom-checklist-90-R questionnaire, for groups A and B.
The mean scores of each of the 10 subscales of Symptom-checklist-90-R will be calculated. A global severity index is computed as the average score of all 90 items. A higher score indicates a worse outcome.Psychometric evaluation (Pichot's fatigue scale) At least 3 months after the initiation of DTG/BIC Psychometric evaluation through Pichot's fatigue scale questionnaire, for groups A and B.
Pichot's fatigue scale scores answers between 0 and 32. A higher score means a worse outcome.Change of psychometric evaluation (Pittsburgh Sleep Quality Index) Baseline and at 6 months Change from baseline Pittsburgh Sleep Quality Index at 6 month after treatment initiation, for groups D and E.
Pittsburgh Sleep Quality Index scores answers from 0 to 21. A higher score means a worse outcome.Dolutegravir and bictegravir through concentration 24 hours post last dose Measurement of drug through concentration for groups A, B, D and E
Dolutegravir and bictegravir intracellular concentration 24 hours post last dose Measurement of drug intracellular concentration for groups A, B, D and E
Viral replication At least 3 months after the initiation of DTG/BIC Viral replication measured for groups A, B, D and E
Microbiota profile under treatment At least 6 months after the initiation of DTG/BIC Determination microbiota profile for groups A, B, C, D and E
Change of psychometric evaluation (Symptom-checklist-90-R) Baseline and at 6 months Change from baseline Symptom-checklist-90-R at 6 month after treatment initiation, for groups D and E.
The mean scores of each of the 10 subscales of Symptom-checklist-90-R will be calculated. A global severity index is computed as the average score of all 90 items. A higher score indicates a worse outcome.Psychometric evaluation (Pittsburgh Sleep Quality Index) At least 3 months after the initiation of DTG/BIC Psychometric evaluation through Pittsburgh Sleep Quality Index questionnaire, for groups A and B.
Pittsburgh Sleep Quality Index scores answers from 0 to 21. A higher score means a worse outcome.Change of psychometric evaluation (Pichot's fatigue scale) Baseline and at 6 months Change from baseline Pichot's fatigue scale at 6 month after treatment initiation, for groups D and E.
Pichot's fatigue scale scores answers between 0 and 32. A higher score means a worse outcome.Psychometric evaluation (Hospital Anxiety and Depression Scale) At least 3 months after the initiation of DTG/BIC Psychometric evaluation through Hospital Anxiety and Depression Scale questionnaire, for groups A and B.
Hospital Anxiety and Depression Scale scores answers between 0 and 21 for its two compoinents, anxiety and depression. A higher score means a worse outcome.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Belgium