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

Phase 2

Not yet recruiting

• Conditions: HBV Coinfection; HIV Infections
• Interventions: 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)

• Registration Number: NCT06338826
• Lead Sponsor: ANRS, Emerging Infectious Diseases

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-27
• Study First Submitted QC: 2024-03-27
• Study First Posted: 2024-04-01
• Status Verified: 2025-01
• Study Start: 2025-02-01
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-05
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 140

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm 2 (T4):	TDF - 245mg or TAF -25mg associated to 3TC - 300mg or FTC - 200mg and a NNRTI or PI/r or INSTI	- Arm 2 (T4): Relief from previous triple antiviral therapy (containing TDF or TAF) on 4 out of 7 consecutive days
Arm 3 (B7)	Dual therapy with 3TC in combination with DTG or ritonavir-boosted Darunavir (rDVR)	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

Primary Outcome Measures

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

Secondary Outcome Measures

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