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

• Status: Active, not recruiting
• Trial end date: 2025-04-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Ghent
• Collaborator: ViiV Healthcare

Criteria

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)