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

Official title

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

Overview

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

Interventions

• 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
• 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

Primary outcome measures

• The proportion of participants with HBV virological failure at 96 weeks. [Time frame: 96 weeks]

Secondary outcome measures (12)

• • HBV virological success rate at 48 weeks [Time frame: at Week 48]
• • HIV virological success rate at 48 and 96 weeks [Time frame: At week 48 and week 96]
• • Time to virological failure (rebound HBV and/or HIV viral load) [Time frame: between Week 0 and Week96]
• • The rate of participants with at least one HBV viral load blip until W48 and until W96 [Time frame: At week 48 and week 96]
• • Selection of HBV resistance mutations at the time of virological failure [Time frame: 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 [Time frame: At week 48 and week 96]
• • Evolution of CD4 from W0 to W48 and W96 [Time frame: Week 0 to Week 48 and week 96]
• • Evolution of total cholesterol from W0 to W48 and W96 [Time frame: from Week 0 to Week 48 and Week 96]
• • Evaluation of the adherence by self-reported questionnaire [Time frame: 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 [Time frame: 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 [Time frame: Week 0 to Week 48 and week 96]
• Evolution of the CD4/CD8 ratio from W0 to W48 and W96 [Time frame: Week 0 to Week 48 and week 96]

Eligibility criteria

Inclusion criteria

• 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);
• 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);
• CD4 lymphocytes > 250/mm3 at pre-inclusion;
• ALT < 3N at pre-inclusion;
• 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;
• 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

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06338826 · ANRS0250s-BI-LIGHT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗