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.
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.
Study Type
OBSERVATIONAL
Enrollment
180
Dolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up.
Bictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
Patient having discontinued dolutegravir will be included and samples (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
Cliniques universitaires Saint-Luc
Brussels, Belgium
Dolutegravir and bictegravir through concentration
Measurement of drug through concentration for groups A, B, D and E
Time frame: 24 hours post last dose
Dolutegravir and bictegravir intracellular concentration
Measurement of drug intracellular concentration for groups A, B, D and E
Time frame: 24 hours post last dose
Viral replication
Viral replication measured for groups A, B, D and E
Time frame: At least 3 months after the initiation of DTG/BIC
Microbiota profile under treatment
Determination microbiota profile for groups A, B, C, D and E
Time frame: At least 6 months after the initiation of DTG/BIC
Change of microbiota profile
Change from baseline microbiota profile at 6 month after treatment initiation, for groups D and E
Time frame: Baseline and at 6 months
Change in weight
Overall weight change between treatment initiation through study completion
Time frame: Through study completion, an average of 1 year
Psychometric evaluation (Symptom-checklist-90-R)
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.
Time frame: At least 3 months after the initiation of DTG/BIC
Change of psychometric evaluation (Symptom-checklist-90-R)
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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
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
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.
Time frame: Baseline and at 6 months
Psychometric evaluation (Pittsburgh Sleep Quality Index)
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.
Time frame: At least 3 months after the initiation of DTG/BIC
Change of psychometric evaluation (Pittsburgh Sleep Quality Index)
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.
Time frame: Baseline and at 6 months
Psychometric evaluation (Pichot's fatigue scale)
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.
Time frame: At least 3 months after the initiation of DTG/BIC
Change of psychometric evaluation (Pichot's fatigue scale)
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.
Time frame: Baseline and at 6 months
Psychometric evaluation (Hospital Anxiety and Depression Scale)
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.
Time frame: At least 3 months after the initiation of DTG/BIC
Change of psychometric evaluation (Hospital Anxiety and Depression Scale)
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.
Time frame: Baseline and at 6 months