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

NCT06338826 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ANRS0250s-BI-LIGHT
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

HIV Infections; HBV Coinfection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• • HBV virological success rate at 48 weeks

  at Week 48

• • HIV virological success rate at 48 and 96 weeks

  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

  At week 48 and week 96

• • Selection of HBV resistance mutations at the time of virological failure

  between Week 0 and Week 96

Study Arms (3)

Arm 1

NO INTERVENTION

\- Arm 1 (reference arm): Continuation of continuous (7 days/week) triple antiviral therapy including TDF or TAF

Arm 2 (T4):

EXPERIMENTAL

\- 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

Arm 3 (B7)

EXPERIMENTAL

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)

Interventions

TDF - 245mg or TAF -25mg associated to 3TC - 300mg or FTC - 200mg and a NNRTI or PI/r or INSTI DRUG

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

Arm 2 (T4):

Dual therapy with 3TC in combination with DTG or ritonavir-boosted Darunavir (rDVR) DRUG

dual therapy without TDF or TAF but including 3TC in combination with Dolutegravir (DTG) or ritonavir-boosted Darunavir (rDVR

Arm 3 (B7)

Eligibility Criteria

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

You may qualify if:

• HIV-1-HBV co-infection (positive HIV-1 serology associated with 2 positive HBsAg serologies within more than 6 months);
• Age ≥ 18 years
• Fibroscan less than 6 months \< 9kPa
• 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;
• 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);
• 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);
• 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);
• For women of childbearing potential, negative pregnancy test and commitment to use effective contraception throughout the trial;
• Person affiliated with or benefiting from a social security system;

You may not qualify if:

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

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

MeSH Terms

Conditions

HIV Infections

Interventions

Racivir; dolutegravir

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

Study Officials

• Julie Bottero

  Bicetre Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fatoumata COULIBALY

CONTACT

0144236110; fatoumata.coulibaly@anrs.fr

Karine Amat

CONTACT

karine.amat@fondation-imea.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Interventional, sequential, Phase IIA equivalent, multicenter, open-label, randomized, non-comparative study evaluating, for 96 weeks, the safety in terms of HBV virological control of 2 antiviral therapy relief strategies, in HIV-1 and HBV co-infected patients with prolonged virological success (undetectable HIV-1 and HBV viral loads for ≥ 2 years) and on unmodified antiviral therapy for ≥ 1 year. Participants will be randomized 1:2:2 into 3 parallel arms: * Arm 1 (reference arm): Continuation of continuous (7 days/week) triple antiviral therapy including TDF or TAF * Arm 2 (T4): Relief from previous triple antiviral therapy (containing TDF or TAF) on 4 out of 7 consecutive days * 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). The choice of dual therapy is left to the discretion of the investigator.

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: April 1, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 5, 2025

Record last verified: 2025-01