Clinical trial NCT06338826: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HIV Infections
HBV Coinfection
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2024-04-01
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: The proportion of participants with HBV virological failure at 96 weeks.
timeFrame: 96 weeks
Secondary outcomes:
measure: • HBV virological success rate at 48 weeks
timeFrame: at Week 48
measure: • HIV virological success rate at 48 and 96 weeks
timeFrame: At week 48 and week 96
measure: • Time to virological failure (rebound HBV and/or HIV viral load)
timeFrame: between Week 0 and Week96
measure: • The rate of participants with at least one HBV viral load blip until W48 and until W96
timeFrame: At week 48 and week 96
measure: • Selection of HBV resistance mutations at the time of virological failure
timeFrame: between Week 0 and Week 96
measure: • 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
timeFrame: At week 48 and week 96
measure: • Evolution of CD4 from W0 to W48 and W96
timeFrame: Week 0 to Week 48 and week 96
measure: • Evolution of total cholesterol from W0 to W48 and W96
timeFrame: from Week 0 to Week 48 and Week 96
measure: • Evaluation of the adherence by self-reported questionnaire
timeFrame: at Week 0, Week 12, Week 24, Week 48, Week 72 and Week 96
measure: • Evaluation of quality of life using the Pro-Qol self-questionnaire
timeFrame: at Week 0, Week 12, Week 24, Week 48, Week 72 and Week 96
measure: Evolution of CD8 T lymphocytes from W0 to W48 and W96
timeFrame: Week 0 to Week 48 and week 96
measure: Evolution of the CD4/CD8 ratio from W0 to W48 and W96
timeFrame: Week 0 to Week 48 and week 96
measure: Evolution of LDL-c from W0 to W48 and W96
timeFrame: from Week 0 to Week 48 and Week 96
measure: Evolution of HDL-c from W0 to W48 and W96
timeFrame: from Week 0 to Week 48 and Week 96
measure: Evolution of triglycerides from W0 to W48 and W96
timeFrame: from Week 0 to Week 48 and Week 96
measure: Evolution of fasting blood sugar from W0 to W48 and W96
timeFrame: from Week 0 to Week 48 and Week 96
measure: HBV virological success rate at 96 weeks between arms
timeFrame: at Week 96
Other outcomes:
Locations:
Study officials:
affiliation: Bicetre Hospital
name: Julie Bottero
role: PRINCIPAL_INVESTIGATOR
References: