HIV Infections
Conditions
Keywords
integrase strand transfer inhibitors, hiv, dolutegravir, bictegravir
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.
Interventions
DRUGDolutegravir
Dolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up.
DRUGBictegravir
Bictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
Sponsors
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 microbiota profile | Baseline and at 6 months | Change from baseline microbiota profile at 6 month after treatment initiation, for groups D and E |
| Change in weight | Through study completion, an average of 1 year | Overall weight change between treatment initiation through study completion |
| 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. |
| 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 (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. |
| 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 (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. |
| 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. |
Countries
Belgium
Outcome results
None listed