Gut Microbiota, PGx and INSTIs Response

NCT04805944 | Completed

• 1 other identifier: INSTI
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Keywords

integrase strand transfer inhibitors; hiv; dolutegravir; bictegravir

Outcome Measures

Primary Outcomes (14)

• Dolutegravir and bictegravir through concentration

  Measurement of drug through concentration for groups A, B, D and E

  24 hours post last dose

• Dolutegravir and bictegravir intracellular concentration

  Measurement of drug intracellular concentration for groups A, B, D and E

  24 hours post last dose

• Viral replication

  Viral replication measured for groups A, B, D and E

  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

  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

  Baseline and at 6 months

• Change in weight

  Overall weight change between treatment initiation through study completion

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Baseline and at 6 months

Study Arms (5)

DTG treated (A)

80 HIV-infected adults treated with dolutegravir (as a component of their usual provider-prescribed antiretroviral regimen)

Drug: Dolutegravir

BIC treated (B)

30 HIV-infected adults treated with bictegravir (as a component of their usual provider-prescribed antiretroviral regimen)

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)

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

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

Drug: Bictegravir

Interventions

Dolutegravir DRUG

Dolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up.

DTG treated (A)

Bictegravir DRUG

Bictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.

BIC treated (B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may not qualify if:

• Liver failure (Child-Pugh A, B or C)

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (1)

Cliniques universitaires Saint-Luc

Brussels, Belgium

Location

Related Publications (1)

• 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.

  PMID: 40592975 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood, Stools

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

dolutegravir; bictegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Study Officials

• Leïla Belkhir, MD, PhD

  Cliniques universitaires Saint-Luc; UCLouvain/IREC/LTAP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 18, 2021
• Study Start: March 10, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: May 10, 2024

Record last verified: 2024-05

Locations

BE (1)