Study Evaluating the Safety, in Terms of HBV Virological Control At 96 Weeks, of 2 Antiviral Treatment Relief Strategies, in Patients Co-infected with the HIV-1 and HBV Viruses (BI-LIGHT)

Interventional, Multicenter, Open-label, Randomized, Non-comparative Trial Evaluating the Safety, in Terms of HBV Virological Control At 96 Weeks, of 2 Antiviral Treatment Relief Strategies, in Patients Co-infected with the HIV-1 and HBV Viruses

The main objective of this study is to evaluate at 96 weeks the safety with respect to hepatitis B control of 2 treatment reduction strategies for patients with previously controlled HIV-HBV co-infection on continuous triple therapy

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infections; HBV Coinfection
• Intervention / Treatment: Drug: TDF - 245mg or TAF -25mg associated to 3TC - 300mg or FTC - 200mg and a NNRTI or PI/r or INSTI; Drug: Dual therapy with 3TC in combination with DTG or ritonavir-boosted Darunavir (rDVR)

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fatoumata Coulibaly; Phone Number: +33 0144236110; Email: fatoumata.coulibaly@anrs.fr
• Study Contact Backup: Name: Karine Amat; Email: karine.amat@fondation-imea.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. HIV-1-HBV co-infection (positive HIV-1 serology associated with 2 positive HBsAg serologies within more than 6 months);
2. Age ≥ 18 years
3. Fibroscan less than 6 months < 9kPa

4. Current daily antiretroviral tritherapy not modified for ≥ 12 months must including tenofovir disoproxil fumarate (TDF) 245mg or tenofovir alafenamide fumarate (TAF -25mg) associated to lamivudine (3TC - 300mg) or emtricitabine (FTC - 200mg) and a NNRTI or PI/r or INSTI to choose from

   • NNRTI = efavirenz, rilpivirine, etravirine, doravirine
   • PI/r = atazanavir/r ou darunavir/r
   • INSTI = bictegravir, dolutegravir, elvitegravir/cobicistat, raltegravir;
5. Absence of documented HBV and HIV genotypic resistance compromising virologic control of any of the maintenance strategies. Patients with no genotypic history may be included);
6. HIV CV < 50cp/ml for ≥ 2 years (only 1 annual blip allowed if HIV CV < 200cp/ml and previous and subsequent viral loads are undetectable);
7. HBV CV < 10 IU/ml for ≥ 2 years (only 1 annual blip allowed if HBV CV < 200IU/ml and if previous and subsequent viral loads are undetectable);
8. Have ≥ 3 available measurements of HIV CV < 50cp/ml and HBV CV < 10 IU/mL over the past 24 months (including that of pre-inclusion);
9. CD4 lymphocytes > 250/mm3 at pre-inclusion;
10. ALT < 3N at pre-inclusion;
11. For women of childbearing potential, negative pregnancy test and commitment to use effective contraception throughout the trial;
12. Person affiliated with or benefiting from a social security system;
13. Free, informed, written consent, signed by the person and the investigator at the latest on the day of inclusion and before any examination carried out as part of the study (article L1122-1-1 of the Public Health Code)

Exclusion Criteria:

1. HIV-2 infection;
2. HIV and/or HBV genotype not compatible with dual therapy DTG-3TC or DRVr-3TC;
3. HBeAg+;
4. Fibrosis history at stage F3-F4 in pre-therapy evaluated by PBH, fibrotest and/or fibroscan with a value of Elastometry ≥ 9kPa;
5. Chronic active viral hepatitis C (HCV RNA positive);
6. Delta co-infection;
7. Alcohol consumption > 14 units/week for women and 21 units/week for men;
8. Current treatment with chemo- or immunotherapy (including interferon or interleukins);
9. Active opportunistic infection or acute treatment for opportunistic infection;
10. Any condition (drug use, neurological, neuropsychiatric, etc.) that, in the judgment of the investigator, may compromise patient compliance and adherence to the protocol;
11. Pregnant or breastfeeding woman or refusal of contraception;
12. Major incapacity, legal protection, guardianship or curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Arm 1; - Arm 1 (reference arm): Continuation of continuous (7 days/week) triple antiviral therapy including TDF or TAF
Experimental: Arm 2 (T4): - Arm 2 (T4): Relief from previous triple antiviral therapy (containing TDF or TAF) on 4 out of 7 consecutive days	Drug: TDF - 245mg or TAF -25mg associated to 3TC - 300mg or FTC - 200mg and a NNRTI or PI/r or INSTI; The study will include patients under current daily antiretroviral tritherapy not modified for ≥ 12 months must including tenofovir disoproxil fumarate (TDF) 245mg or tenofovir alafenamide fumarate (TAF -25mg) associated to lamivudine (3TC - 300mg) or emtricitabine (FTC - 200mg) and a NNRTI or PI/r or INSTI to choose from; NNRTI = efavirenz, rilpivirine, etravirine, doravirine; PI/r = atazanavir/r ou darunavir/r; INSTI = bictegravir, dolutegravir, elvitegravir/cobicistat, raltegravir
Experimental: Arm 3 (B7); Switch from prior triple antiviral therapy (containing TDF or TAF) to continuous dual therapy without TDF or TAF but including 3TC in combination with Dolutegravir (DTG) or ritonavir-boosted Darunavir (rDVR	Drug: Dual therapy with 3TC in combination with DTG or ritonavir-boosted Darunavir (rDVR); dual therapy without TDF or TAF but including 3TC in combination with Dolutegravir (DTG) or ritonavir-boosted Darunavir (rDVR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with HBV virological failure at 96 weeks.	HBV virologoical failure is defined by 2 successive varial load ≥ 10UI/ml	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• HBV virological success rate at 48 weeks	HBV virological success is defined by a viral load ≤10 UI/ml	at Week 48
• HIV virological success rate at 48 and 96 weeks	HIV virological success is defined by a viral load ≤ 50 cp/ml	At week 48 and week 96
• Time to virological failure (rebound HBV and/or HIV viral load)		between Week 0 and Week96
• The rate of participants with at least one HBV viral load blip until W48 and until W96	a blip is defined by a HBV viral load >10UI/mL followed by a control value ≤ 10UIml	At week 48 and week 96
• Selection of HBV resistance mutations at the time of virological failure		between Week 0 and Week 96
• Incidence of grade 3 or higher adverse events of grade 3 or higher, incidence of adverse events and incidence of strategy discontinuation of the strategy at W48 and W96		At week 48 and week 96
• Evolution of CD4 from W0 to W48 and W96		Week 0 to Week 48 and week 96
• Evolution of total cholesterol from W0 to W48 and W96		from Week 0 to Week 48 and Week 96
• Evaluation of the adherence by self-reported questionnaire	without analysis scale	at Week 0, Week 12, Week 24, Week 48, Week 72 and Week 96
• Evaluation of quality of life using the Pro-Qol self-questionnaire	without analysis scale	at Week 0, Week 12, Week 24, Week 48, Week 72 and Week 96
Evolution of CD8 T lymphocytes from W0 to W48 and W96		Week 0 to Week 48 and week 96
Evolution of the CD4/CD8 ratio from W0 to W48 and W96		Week 0 to Week 48 and week 96
Evolution of LDL-c from W0 to W48 and W96		from Week 0 to Week 48 and Week 96
Evolution of HDL-c from W0 to W48 and W96		from Week 0 to Week 48 and Week 96
Evolution of triglycerides from W0 to W48 and W96		from Week 0 to Week 48 and Week 96
Evolution of fasting blood sugar from W0 to W48 and W96		from Week 0 to Week 48 and Week 96
HBV virological success rate at 96 weeks between arms	HBV virological success is defined by a viral load ≤10 UI/ml	at Week 96

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Julie Bottero, Bicetre Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Coinfection; Viral Protease Inhibitors; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Cytochrome P-450 Enzyme Inhibitors; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Darunavir; Ritonavir; Lamivudine
• Other Study ID Numbers: ANRS0250s-BI-LIGHT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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