2DR Versus 3DR in a Prospective Randomized Controlled Switch Trial

Sponsor
University Hospital, Ghent (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04553081
Collaborator
ViiV Healthcare (Industry)
134
1
2
59.1
2.3

Study Details

Study Description

Brief Summary

The aim of this study is to monitor virological and immunological markers in participants who are switching from a classic triple drug regimen (3DR) to dual therapy (2DR). We aim to monitor whether this has an influence on different parameters such as severity of HIV disease (evaluated by viral load and viral reservoir size), presence of non-AIDS related health complications, impact the phenotype and function of the immune system.

By conducting this study we want to assess whether switching from 3DR to 2DR implies an increased risk for 'subclinical' failure. We especially want to make sure that this switch does not increase the HIV reservoir, does not increase inflammation or immune exhaustion in patients living with HIV and that it can be considered as a safe long term alternative for the classic 3DR.

The primary objective is to demonstrate non inferiority at W48 of the 2DR DTG/3TC (Dovato) regimen compared to BIC/TAF/FTC (Biktarvy) in terms of the amount of intact replication competent HIV sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by IPDA, present in blood CD4 cells.

Condition or Disease Intervention/Treatment Phase
  • Drug: Dual versus triple therapy in treatment of HIV-1 infection.
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
134 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Virological and Immunological Assessment in HIV Positive Participants on 2DR Versus 3DR in a Prospective Randomized Controlled Switch Trial
Actual Study Start Date :
May 26, 2020
Anticipated Primary Completion Date :
May 31, 2023
Anticipated Study Completion Date :
Apr 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Dovato

We aim to include 134 adult HIV-infected patients with HIV RNA < 50 copies/mL for at least 3 months on any stable 2nd generation integrase based triple therapy antiretroviral regimen. Patients will be randomized 1:2 to switch to or stay on the triple regimen BIC/TAF/FTC (Biktarvy) (N=45) or to switch to the dual regimen DTG/3TC (Dovato) (N=89).

Drug: Dual versus triple therapy in treatment of HIV-1 infection.
cfr arm decsription

Active Comparator: Biktarvy

We aim to include 134 adult HIV-infected patients with HIV RNA < 50 copies/mL for at least 3 months on any stable 2nd generation integrase based triple therapy antiretroviral regimen. Patients will be randomized 1:2 to switch to or stay on the triple regimen BIC/TAF/FTC (Biktarvy) (N=45) or to switch to the dual regimen DTG/3TC (Dovato) (N=89).

Drug: Dual versus triple therapy in treatment of HIV-1 infection.
cfr arm decsription

Outcome Measures

Primary Outcome Measures

  1. Difference in amount of intact replication-competent HIV-1 sequences in CD4 cells between 2 regimens [48 weeks]

    The primary objective is to demonstrate non inferiority at W48 of the 2DR DTG/3TC (Dovato) regimen compared to BIC/TAF/FTC (Biktarvy) in HIV-1 infected individuals in terms of the amount of intact replication-competent HIV-1 sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by IPDA, present in blood CD4 cells.

Secondary Outcome Measures

  1. Full length sequencing of the virus [144 weeks]

    Full length sequencing of the virus at baseline, W48 and W144

  2. Quantification of interleukin-6 (IL-6) [144 weeks]

    Quantification of IL-6 at baseline, W48 and W144

  3. Quantification of high-sensitivity C-reactive protein (hs-CRP) [144 weeks]

    Quantification of hs-CRP at baseline, W48 and W144

  4. Quantification of D-Dimers [144 weeks]

    Quantification of D-Dimers at baseline, W48 and W144

  5. Quantification of Human Leukocyte Antigen - DR isotype (HLA-DR) [144 weeks]

    Quantification of HLA-DR at baseline, W48 and W144

  6. Quantification of cluster of differentiation 38 (CD38) [144 weeks]

    Quantification of CD38 on both cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) immune cells at baseline, W48 and W144

  7. Quantification of soluble cluster of differentiation 27 (sCD27) [144 weeks]

    Quantification of sCD27 at baseline, W48 and W144

  8. Quantification of soluble cluster of differentiation 40 (sCD40) [144 weeks]

    Quantification of sCD40 at baseline, W48 and W144

  9. Quantification of programmed cell death protein 1 (PD-1) [144 weeks]

    Quantification of the T cell exhaustion marker PD-1 at baseline, W48 and W144

  10. Quantification of cluster of differentiation 28 (CD28) [144 weeks]

    Quantification of the T cell exhaustion marker CD28 at baseline, W48 and W144

  11. Quantification of cluster of differentiation 57 (CD57) [144 weeks]

    Quantification of the T cell exhaustion marker CD57 at baseline, W48 and W144

  12. Quantification of soluble cluster of differentiation 14 (sCD14) [144 weeks]

    Quantification of markers of microbial translocation sCD14 at baseline, W48 and W144

  13. Quantification of CD4/CD8 ratio [144 weeks]

    Quantification of CD4/CD8 ratio at baseline, W48 and W144

  14. Incidence of metabolic syndrome [144 weeks]

    Metabolic health will be assessed through incidence of metabolic syndrome at baseline, W48 and W144

  15. Weight/body mass index (BMI) change [144 weeks]

    Metabolic health will be assessed through weight/BMI change at baseline, W48 and W144

  16. Waist circumference [144 weeks]

    Metabolic health will be assessed through waist circumference at baseline, W48 and W144

  17. Insuline resistance [144 weeks]

    Metabolic health will be assessed through insuline resistance at baseline, W48 and W144

  18. Dual-energy x-ray absorptiometry (DXA) [144 weeks]

    Bone mineral density will be assessed through DXA at baseline, W48 and W144

  19. FibroScans [144 weeks]

    Fat distribution will be assessed through FibroScans at baseline, W48 and W144

  20. Switch questionnaire [144 weeks]

    The impact of switching will be assessed through a patient switch questionnaire at baseline, W48 and W144

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Age = or >18 years.

  • Ability and willingness to provide written informed consent.

  • Ability to attend the complete schedule of assessments and patient visits.

  • Ability and willingness to have blood samples collected and stored indefinitely and used for various research purposes.

  • HIV RNA < 50 copies/mL for at least 3 months on a 2nd generation INSTI based regimen.

  • Females of childbearing potential should be on effective contraception

Exclusion Criteria:
  • Current presence of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification).

  • Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (seroconversion= HBV antigen or viral load negative and positive HBV surface antibody).

  • Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry.

  • Pregnancy or breastfeeding.

  • Patients unable to understand the study protocol or any other condition that in the investigator's opinion may compromise compliance with the study protocol

  • Decompensated liver cirrhosis (Child-Pugh B/C)

  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones)

  • Psychiatric and psychological disorders, which in the opinion of the investigator, will interfere with the trial conduct or safety of the participant.

  • Previous participation in a trial evaluating an immune modulating agent.

  • Active drug or alcohol use/addiction such that, in the opinion of the site investigator, would interfere with adherence to study requirements.

  • Treatment failure on an integrase inhibitor containing regimen and reported baseline resistance

  • Creatinine Clearance <50

  • Tuberculosis treatment

  • Documented M184V

  • Previous virological failure >200 copies/mL on NRTI

  • Subjects with history or presence of allergy to any of the study drugs or their components

  • ALT >5 times the ULN, OR ALT >3xULN and bilirubin >1.5xULN (with >35% direct bilirubin)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Ghent University Hospital Ghent Belgium 9000

Sponsors and Collaborators

  • University Hospital, Ghent
  • ViiV Healthcare

Investigators

  • Principal Investigator: Linos Vandekerckhove, University Hospital, Ghent

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT04553081
Other Study ID Numbers:
  • BC-7052
First Posted:
Sep 17, 2020
Last Update Posted:
Nov 1, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by University Hospital, Ghent

Study Results

No Results Posted as of Nov 1, 2021