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)

ANRS, Emerging Infectious Diseases

Status and phase: Not yet enrolling; Phase 2

Conditions: HBV Coinfection; HIV Infections

Treatments: Drug: Dual therapy with 3TC in combination with DTG or ritonavir-boosted Darunavir (rDVR); Drug: TDF - 245mg or TAF -25mg associated to 3TC - 300mg or FTC - 200mg and a NNRTI or PI/r or INSTI

Study type: Interventional

Funder types: Other

Identifiers

NCT06338826

ANRS0250s-BI-LIGHT

Details and patient eligibility

About

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

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

---

140 participants in 3 patient groups

Arm 1

No Intervention group

Description:

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

Arm 2 (T4):

Experimental group

Description:

- Arm 2 (T4): Relief from previous triple antiviral therapy (containing TDF or TAF) on 4 out of 7 consecutive days

Treatment:

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 group

Description:

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

Treatment:

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