HIV InfectionsNCT04805944
Gut Microbiota, PGx and INSTIs Response
An observational study of HIV Infections, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Dolutegravir and Bictegravir
- How many people
- 180 participants
- Where
- 1 siteBelgium
- Study dates
- 10 Mar 2021to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Gut Microbiota, Pharmacogenetics and Integrase Strand Transfer Inhibitors Response
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.
Read the 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.
- Conditions
- HIV Infections
- Being tested
- Dolutegravir, Bictegravir
- Keywords
- integrase strand transfer inhibitors, hiv, dolutegravir, bictegravir
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Dolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up.
BictegravirDrug
Bictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
DolutegravirDrug
Patient having discontinued dolutegravir will be included and samples (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
DolutegravirDrug
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
BictegravirDrug
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
| Study group | Role | What they receive |
|---|---|---|
| DTG treated (A) | 80 HIV-infected adults treated with dolutegravir (as a component of their usual provider-prescribed antiretroviral regimen) Receives: Drug: Dolutegravir | |
| BIC treated (B) | 30 HIV-infected adults treated with bictegravir (as a component of their usual provider-prescribed antiretroviral regimen) Receives: Drug: Bictegravir | |
| DTG discontinued due to neuropsychiatric adverse event (C) | 50 HIV-infected adults having stopped dolutegravir due to neuropsychiatric adverse effects (insomnia, depression, anxiety) Receives: Drug: Dolutegravir | |
| Shifting to DTG (D) | 20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing dolutegravir Receives: Drug: Dolutegravir | |
| Shifting to BIC (E) | 20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing bictegravir Receives: Drug: Bictegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dolutegravir and bictegravir through concentration
Measurement of drug through concentration for groups A, B, D and E
Measured: 24 hours post last dose
Dolutegravir and bictegravir intracellular concentration
Measurement of drug intracellular concentration for groups A, B, D and E
Measured: 24 hours post last dose
Viral replication
Viral replication measured for groups A, B, D and E
Measured: 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
Measured: 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
Measured: Baseline and at 6 months
Change in weight
Overall weight change between treatment initiation through study completion
Measured: 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.
Measured: At least 3 months after the initiation of DTG/BIC
Change of psychometric evaluation (Symptom-checklist-90-R)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2021
- Study start10 Mar 2021
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Leïla Belkhir, MD, PhD, Principal investigator, Cliniques universitaires Saint-Luc; UCLouvain/IREC/LTAP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04805944
- Sponsor's protocol ID
- INSTI
- Status last verified
- May 2024
- First submitted
- 8 Mar 2021
- Last updated
- 10 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
De Greef J, Nguyen KN, Van Hul M, Puel A, Yombi JC, Vandercam B, Vincent A, Elens L, Belkhir L, Haufroid V, Cani PD. Associations between weight gain, integrase inhibitors antiretroviral agents, and gut microbiome in people living with HIV: a cross-sectional study. Sci Rep. 2025 Jul 2;15(1):22603. doi: 10.1038/s41598-025-06500-0.
PubMed 40592975
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Microbiota, Pharmacogenetics and Integrase Strand Transfer Inhibitors Response
- ClinicalTrials.gov ID
- NCT04805944
- Acronym / sponsor ID
- INSTI
- Conditions
- HIV Infections
- Keywords
- integrase strand transfer inhibitors, hiv, dolutegravir, bictegravir
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de LouvainUniversity, hospital or other
- Study start
- 10 Mar 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 18 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| DTG treated (A) | – | Drug: Dolutegravir80 HIV-infected adults treated with dolutegravir (as a component of their usual provider-prescribed antiretroviral regimen) |
| BIC treated (B) | – | Drug: Bictegravir30 HIV-infected adults treated with bictegravir (as a component of their usual provider-prescribed antiretroviral regimen) |
| DTG discontinued due to neuropsychiatric adverse event (C) | – | Drug: Dolutegravir50 HIV-infected adults having stopped dolutegravir due to neuropsychiatric adverse effects (insomnia, depression, anxiety) |
| Shifting to DTG (D) | – | Drug: Dolutegravir20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing dolutegravir |
| Shifting to BIC (E) | – | Drug: Bictegravir20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing bictegravir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DolutegravirDolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up. | Drug | DTG treated (A) |
| BictegravirBictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up. | Drug | BIC treated (B) |
| DolutegravirPatient having discontinued dolutegravir will be included and samples (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up. | Drug | DTG discontinued due to neuropsychiatric adverse event (C) |
| DolutegravirPatients 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 | Drug | Shifting to DTG (D) |
| BictegravirPatients 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 | Drug | Shifting to BIC (E) |
Primary outcome
Dolutegravir and bictegravir through concentration
Time frame: 24 hours post last dose
Measurement of drug through concentration for groups A, B, D and E
Dolutegravir and bictegravir intracellular concentration
Time frame: 24 hours post last dose
Measurement of drug intracellular concentration for groups A, B, D and E
Viral replication
Time frame: At least 3 months after the initiation of DTG/BIC
Viral replication measured for groups A, B, D and E
Microbiota profile under treatment
Time frame: 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
Time frame: Baseline and at 6 months
Change from baseline microbiota profile at 6 month after treatment initiation, for groups D and E
Change in weight
Time frame: Through study completion, an average of 1 year
Overall weight change between treatment initiation through study completion
Psychometric evaluation (Symptom-checklist-90-R)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- Derived from this study: PubMed 40592975De Greef J, Nguyen KN, Van Hul M, Puel A, Yombi JC, Vandercam B, Vincent A, Elens L, Belkhir L, Haufroid V, Cani PD. Associations between weight gain, integrase inhibitors antiretroviral agents, and gut microbiome in people living with HIV: a cross-sectional study. Sci Rep. 2025 Jul 2;15(1):22603. doi: 10.1038/s41598-025-06500-0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leïla Belkhir, MD, PhD principal investigator
Cliniques universitaires Saint-Luc; UCLouvain/IREC/LTAP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infections, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dolutegravir and bictegravir through concentration (time frame: 24 hours post last dose). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04805944, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.