lamivudine, doravirine, tenofovir disoproxil for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- Be at least 18 years of age on the day of signing the informed consent"}
• {"criterion_text":"- Be HIV-1 positive as determined according to national testing strategies"}
• {"criterion_text":"- Have a plasma HIV-1 RNA ≥1000 copies/mL within 30 days prior to the randomization"}
• {"criterion_text":"- Have HIV treatment indication based on physician assessment according to local treatment guidelines"}
• {"criterion_text":"- Be naïve to antiretroviral therapy (ART) for the treatment of HIV infection including investigational antiretroviral agents"}
• {"criterion_text":"- For cisgender women or transgender men of childbearing potential i.e. of childbearing age who are not menopausal, or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or not refraining from sexual activity: negative urinary test for pregnancy and acceptance to use contraceptive methods"}
• {"criterion_text":"- Understand the study procedures and voluntarily agree to participate by giving written informed consent for the trial"}
• {"criterion_text":"- For participants in France, be affiliated to a Social Security program or CMU (Universal Health Cover)"}

Exclusion criteria

• {"criterion_text":"- Has ongoing (pulmonary or extra-pulmonary) active tuberculosis"}
• {"criterion_text":"- Requires or is anticipated to require any of the prohibited or contraindicated medications noted in the trial protocol"}
• {"criterion_text":"- Has significant hypersensitivity or other contraindication to any of the components of the study drugs"}
• {"criterion_text":"- Is pregnant, breastfeeding, or expecting to conceive at any time during the study"}
• {"criterion_text":"- Has any condition, which might, in the investigator’s opinion, compromise the safety of treatment and/or patient’s adherence to study procedures"}
• {"criterion_text":"- Is a person under guardianship or deprived of freedom by a judicial or administrative decision"}
• {"criterion_text":"- Has any other history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study or interfere with the subject’s participation for the full duration of the study, such that it is not in the best interest of the subject to participate"}
• {"criterion_text":"- Is infected with HIV-2 or co-infected with HIV-1 and HIV-2"}
• {"criterion_text":"- Has received cabotegravir long acting or dapivirine pre-exposure prophylaxis (PrEP)"}
• {"criterion_text":"- Has received oral pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) in the past three months or has had no negative HIV-1 serology performed"}
• {"criterion_text":"- Has documented or known resistance or possible resistance to study drugs as defined by the ANRS MIE AC43 Resistance group"}
• {"criterion_text":"- Has the following laboratory values at screening visit, within 30 days prior to the randomization: AST (SGOT) and ALT (SGPT) >4.0 x upper limit of normal (ULN) - estimated glomerular filtration rate at time of screening <60 mL/min/1.73m², based on the CKD-EPI equation"}
• {"criterion_text":"- Has participated in a study with an investigational compound/device within 30 days prior to signing informed consent or anticipates participating in such a study involving an investigational compound/device during the course of this study"}
• {"criterion_text":"- Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study"}

Primary endpoints

• {"endpoint_text":"- Proportion of subjects in virologic success defined as achieving HIV-1 RNA <50 copies/mL at week 48 under allocated treatment using the FDA snapshot algorithm (window period of 42-54 weeks); subjects not achieving viral success will be described according to the FDA snapshot recommendation","definition_or_measurement_approach":"Virologic success defined as HIV-1 RNA <50 copies/mL at week 48 measured using the FDA snapshot algorithm with a window period of 42-54 weeks; subjects not achieving success described per FDA snapshot rules."}

Secondary endpoints

• {"endpoint_text":"- Occurrence of obesity at Week 48 and at Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects with newly measured HOMA≥2 at Week 48 and Week 96 as compared to baseline","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects with hypertension newly detected at Week 48 and Week 96 compared to baseline.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects in virologic success defined as achieving HIV-1 RNA <50 copies/mL at week 96 under allocated treatment using the FDA snapshot algorithm with a window period of 90 to 102 weeks; subjects not achieving viral success will be described according to the FDA snapshot recommendation","definition_or_measurement_approach":"Virologic success at week 96 using FDA snapshot algorithm with window 90-102 weeks."}
• {"endpoint_text":"- Proportion of confirmed virological failures occurring up to Week 48 and up to Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Frequency of HIV-1 drug resistances in participants with a confirmed virological failure","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects achieving HIV 1 RNA<200 copies/mL under allocated treatment at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects achieving HIV 1 RNA<1000 copies/mL under allocated treatment at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Frequency of RT and integrase mutations at baseline and impact on the virological response at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Occurrence of combined overweight and obesity at Week 48 and at Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects with ≥10% absolute weight gain from baseline at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in absolute weight at Week 48 and at Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects with diabetes newly detected at Week 48 and Week 96 compared to baseline","definition_or_measurement_approach":""}
• {"endpoint_text":"- Any adverse event of any grade and those graded 3-4 at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in waist and hip circumferences and waist-to-hip ratio at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in fasting glycemia and insulin at Week 48 and at Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in fasting serum lipids at Week 48 and at Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in estimated glomerular filtration rate at Week 48 and at Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in cardiovascular parameters (blood pressure profile, electrocardiographic and echocardiographic damages) at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in mean patient CAP and LSM measurements at Week 48 and Week 96 and occurrence at Week 48 and Week 96 of: a. Liver steatosis, clinically significant liver fibrosis and cirrhosis b. MASLD and MASH","definition_or_measurement_approach":""}
• {"endpoint_text":"- Changes from baseline in Fib-4, VCTE and FAST scores at Week 48 and Week 96 and presence at baseline or occurrence of CSF defined as Fib-4 ≥2.67 or FAST score > 0.67","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in EQ-5D-3L, HIVTSQ, DASS-21, PSQI, WHOQOL HIV-BREF scores at Week 24, Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of subjects with AIDS (defined as having CDC stage 3/C or WHO stage 4), tuberculosis, IRIS or death at Week 48 and Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- a, b, c, d. DOR, DTG and M9 trough plasma concentration in samples taken pre-dose at Week 4, Week 24, Week 48 and Week 96","definition_or_measurement_approach":"Trough plasma concentrations (pre-dose) measured at Weeks 4, 24, 48, 96 for DOR, DTG and M9."}
• {"endpoint_text":"- Change from baseline in CD4 cell count, CD4 percentage, CD8 cell count, CD8 percentage, CD4/CD8 ratio, at Week 48 and at Week 96","definition_or_measurement_approach":""}
• {"endpoint_text":"- Adherence to ART by (1) pill count (considering a pill count adherence ratio <95% as sub-optimal adherence), (2) 4-days and 1-month recall questions at every trial visit, (3) by TFV-DP quantification in dried blood spots (LC/MS) at Week 48 and Week 96","definition_or_measurement_approach":"Adherence measured by pill count (<95% = sub-optimal), 4-day and 1-month recall, and TFV-DP quantification in dried blood spots at Weeks 48 and 96."}
• {"endpoint_text":"- a. Type and frequency of alleles variants in the gene coding for CYP3A5/4 b. Impact of CYP3A5/4 mutations on pharmacokinetics of DOR, DTG and M9, c. Virological response and side-effects depending on CYP3A5/4 mutations","definition_or_measurement_approach":""}
• {"endpoint_text":"- Assess additional polymorphism of UGT1A1 at baseline","definition_or_measurement_approach":""}
• {"endpoint_text":"- Cost-effectiveness measured by (1) Incremental health benefits of using one regimen compared to the other (in DALYs and QALYs), (2) Incremental economic costs of using one regimen compared to the other (USD), (3) Budget impact of changing from one regimen to the other (USD)","definition_or_measurement_approach":""}
• {"endpoint_text":"- a. Change from baseline in truncal fat distribution at Week 48 and Week 96. b. Change from baseline in adipose tissue markers (adiponectin, leptin) and immune activation markers (sCD14, sCD163) at Week 48 and Week 96. c. Change from baseline (by abdominal subcutaneous surgical biopsy) in fat pathology, gene expression and global transcriptome analysis (RT-PCR and RNAseq) at Week 48","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

15-10-2025

Processing Time Days

427

Number Of Sites

9

Number Of Participants

60

Primary sponsor

Full Name

Inserm

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France