HBV Coinfection, HIV Infections
Conditions
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
Interventions
DRUGTDF - 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
DRUGDual 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
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| HBV virological success rate at 96 weeks between arms | at Week 96 | HBV virological success is defined by a viral load ≤10 UI/ml |
| Evolution of CD8 T lymphocytes from W0 to W48 and W96 | 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 | — |
| Evolution of HDL-c from W0 to W48 and W96 | from Week 0 to Week 48 and Week 96 | — |
| Evolution of triglycerides 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 |
| • 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 |
| Evolution of fasting blood sugar 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 |
| • Selection of HBV resistance mutations at the time of virological failure | 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 | At week 48 and week 96 | — |
| • Evolution of CD4 from W0 to W48 and W96 | Week 0 to Week 48 and week 96 | — |
| • Evolution of total cholesterol from W0 to W48 and W96 | from Week 0 to Week 48 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 |
| • 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 |
| • Time to virological failure (rebound HBV and/or HIV viral load) | between Week 0 and Week96 | — |
Contacts
Primary ContactFatoumata COULIBALY
Backup ContactKarine Amat
Outcome results
None listed