DARUNAVIR for HIV-1 and hepatitis B virus (HBV) co-infection

Inclusion criteria

• {"criterion_text":"- HIV-1-HBV co-infection (positive HIV-1 serology associated with 2 positive HBsAg serologies within more than 6 months)\n- 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)\n- 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)\n- Have ≥ 3 available measurements of HIV CV < 50cp/ml and HBV CV < 10 IU/mL over the past 30 months (including that of pre-inclusion\n- CD4 lymphocytes > 250/mm3 at pre-inclusion\n- Positive Ag HBs HBV serology at pre-inclusion\n- ALT < 3N at pre-inclusion\n- For women of childbearing potential, negative pregnancy test and commitment to use effective contraception throughout the trial\n- Person affiliated with or benefiting from a social security system\n- 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)\n- Age ≥ 18 years\n- Fibroscan less than 6 months < 9kPa\n- 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 \to\tNNRTI = efavirenz, rilpivirine, etravirine, doravirine \to\tPI/r = atazanavir/r ou darunavir/r \to\tINSTI = bictegravir, dolutegravir, elvitegravir/cobicistat, raltegravir\n- 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)"}

Exclusion criteria

• {"criterion_text":"- HIV-2 infection\n- HIV and/or HBV genotype not compatible with dual therapy DTG-3TC or DRVr-3TC\n- HBeAg+.\n- Fibrosis history at stage F3-F4 in pre-therapy evaluated by PBH, fibrotest and/or fibroscan with a value of Elastometry ≥ 9kPa\n- Chronic active viral hepatitis C (HCV RNA positive)\n- Delta co-infection\n- Alcohol consumption > 14 units/week for women and 21 units/week for men\n- Current treatment with chemo- or immunotherapy (including interferon or interleukins)\n- Active opportunistic infection or acute treatment for opportunistic infection\n- Any condition (drug use, neurological, neuropsychiatric, etc.) that, in the judgment of the investigator, may compromise patient compliance and adherence to the protocol\n- Pregnant or breastfeeding woman or refusal of contraception\n- Major incapacity, legal protection, guardianship or curatorship."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint was the proportion of participants with HBV virological failure at 96 weeks. Failure was defined as two successive HBV viral load measurements >10 IU/mL or one HBV viral load measurement above the detection threshold followed by permanent discontinuation of the strategy or follow-up in the trial.","definition_or_measurement_approach":"Failure was defined as two successive HBV viral load measurements >10 IU/mL or one HBV viral load measurement above the detection threshold followed by permanent discontinuation of the strategy or follow-up in the trial."}

Secondary endpoints

• {"endpoint_text":"- •\tHBV virological success rate at 48 weeks","definition_or_measurement_approach":"Absence of virological failure and permanent discontinuation of the strategy (as defined in protocol)."}
• {"endpoint_text":"- •\tHIV virological success rate at 48 and 96 weeks","definition_or_measurement_approach":"HIV virological success rate measured at 48 and 96 weeks (as stated in protocol)."}
• {"endpoint_text":"- •\tTime to virological failure (rebound HBV and/or HIV viral load)","definition_or_measurement_approach":"Time from baseline to occurrence of virological failure/rebound of HBV and/or HIV viral load."}
• {"endpoint_text":"- •\tThe rate of participants with at least one HBV viral load blip until S48 and until S96","definition_or_measurement_approach":"Blip defined as a HBV viral load measurement > 10 IU/mL with surrounding control ≤ 10 IU/mL; rate measured until week 48 and until week 96."}
• {"endpoint_text":"- •\tSelection of HBV resistance mutations at the time of virological failure","definition_or_measurement_approach":"Determination of HBV resistance mutations present at time of virological failure; reported as percentage of participants with resistance mutations."}
• {"endpoint_text":"- •\tIncidence 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","definition_or_measurement_approach":"Incidence of grade ≥3 adverse events, overall adverse events, and incidence of strategy discontinuation at week 48 and week 96."}
• {"endpoint_text":"- •\tEvolution of CD4 and CD8 T lymphocytes, and the CD4/CD8 ratio from W0 to W48 and W96","definition_or_measurement_approach":"Change over time in CD4 and CD8 counts and CD4/CD8 ratio from baseline to weeks 48 and 96."}
• {"endpoint_text":"- •\tEvolution of metabolic parameters (total cholesterol, LDL-c, HDL-c, triglycerides and fasting blood sugar) from W0 to W48 and W96","definition_or_measurement_approach":"Change over time in total cholesterol, LDL-c, HDL-c, triglycerides, and fasting blood glucose from baseline to weeks 48 and 96."}
• {"endpoint_text":"- •\tParticipants' compliance with treatment (self-questionnaire) at S0, S12, S24, S48, S72 and S96","definition_or_measurement_approach":"Self-reported adherence measured by participant self-questionnaire at specified visits (S0, S12, S24, S48, S72, S96)."}
• {"endpoint_text":"- •\tParticipants' quality of life using the Pro-Qol self-questionnaire at S0, S12, S24, S48, S72 and S96","definition_or_measurement_approach":"Quality of life assessed using the Pro-Qol self-questionnaire at specified visits."}
• {"endpoint_text":"- HBV virological success rate at 96 weeks between arms","definition_or_measurement_approach":"Comparison of HBV virological success rates at 96 weeks across treatment arms."}

France

Earliest CTIS Part Ii Submission Date

05-02-2024

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

822

Number Of Sites

21

Number Of Participants

140

Primary sponsor

Full Name

Inserm

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France