Dual Therapy in HIV Patients in 4 Days a Week Versus 7 Days a Week

Study Overview
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Brief Summary
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The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48 the non inferiority of antiretroviral dual therapy taken 4 consecutive days per week versus antiretroviral dual therapy 7/7 days per week in HIV-1 infected patients with controlled viral load under antiretroviral dual therapy.

Detailed Description
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Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48 the non-inferiority of antiretroviral dual therapy taken 4 consecutive days a week versus dual therapy taken 7 days a week, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral dual therapy since 4 months. The non-inferiority margin (delta) is 5%. The randomization will be stratified according to the family of the dual therapy at the moment of the inclusion and according to the participation of the substudy or not. The sample size calculation assumes that the true difference in efficacy between the two arms is zero and that the overall response rate is 97% at week 48. A total of 440 patients (220 per arm) is required to provide 80% power to demonstrate non-inferior efficacy for the 4/7 strategy, compared to the daily dual therapy (7/7), with a two-sided significance level of 5% and a non-inferiority margin (delta) of -5%.

Official Title
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Randomized, Open-label and Multicentric Trial Evaluating the Non-inferiority of Antiretroviral Dual Therapy Taken 4 Consecutive Days Per Week Versus Antiretroviral Dual Therapy 7/7 Days Per Week in HIV-1 Infected Patients With Controlled Viral Load Under Antiretroviral Dual Therapy

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: ARV bitherapie


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infection, coinfection HIV-1/HIV-2 possible Age≥18 years old Current dual therapy unchanged for the last 6 months with Dolutegravir/ Lamivudine or Dolutegravir / Rilpivirine or Darunavir/r / Lamivudine If a genotype is available in the patient medical history; virus must be susceptible to all on going dual therapy. If no ARN genotype available, the patients can be included in the study Viral load (VL) < 50 c/mL in the past twelve months, with at least 3 VL measurements including screening; only one blip < 200 c/mL is authorized in the 6-12 previous months CD4 T cells > 250/mm3 at W-4 Estimated glomerular filtration rate > 60 mL/min (CKD-EPI method) AST et ALT < 3N Haemoglobin > 10 g/dL Platelets > 100 000/mm3 For women of childbearing age, negative pregnancy plasmatic test at W-4 and agree to use efficacy contraception during the study Commitment to use condom prevention and protection during sexual intercourse for the duration of the trial. Social security system coverage (including State Medical Aid-AME, if EC approves it) Informed consent form signed Exclusion Criteria: Infection by HIV-2 Chronic and active Viral B Hepatitis with positive antigen HBs Chronic and active Viral C Hepatitis with treatment expected in the next 48 weeks Concomitant treatment using interferon, interleukins, any other immune-therapy or chemotherapy, antivitamin K+ with co-treatment by booster Concomitant prophylactic or curative treatment for an opportunistic infection All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with study protocol compliance, observance and/or study treatment tolerance Pregnant or breast feeding women Subjects under sauvegarde de justice (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, multicenter, prospective, randomized trial in 2 parallel groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: 4 days/7<br>4 days/7 Patients included in this arm will take their ARV treatment 4 consecutive days per week during 48 weeks. | Drug: ARV bitherapie<br>* Dolutégravir 50mg / Lamivudine 300mg per day Dolutégravir 50mg / Rilpivirine 25mg per day Darunavir/r 800mg/100mg / Lamivudine 300mg per day<br>|
| Active Comparator: Arm 2: 7 days/7<br>Patients included in this arm will take their ARV treatment 7 days per week during 48 weeks | Drug: ARV bitherapie<br>* Dolutégravir 50mg / Lamivudine 300mg per day Dolutégravir 50mg / Rilpivirine 25mg per day Darunavir/r 800mg/100mg / Lamivudine 300mg per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with virological failure at Week 48. | The virological failure is defined by 2 successive viral loads >50 c/mL at 2 to 4 weeks apart or a viral load > 50 c/ml with a definitive stop of the study follow-up or the study strategy | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with therapeutic success until Week 48 |  | Week 48 | 
| Percentage of participants with at least one episode of blip | viral load >50 copies/mL followed by a control value ≤ 50 cp/mL | Week 0 to Week48 | 
| Percentage of participants with a viral load signal detected |  | Week 0 to Week 48 | 
| Evolution of ultrasensitive viral load and total DNA in the PBMC at W0 and W48 | immuno-virological sub-study | Week 0 and Week 48 | 
| Proportion of participants with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by NGS |  | Week 0 to Week 48 | 
| Description of selected mutations at the virological failure |  | Week 0 to Week 48 | 
| Frequency of minority resistant variants archived in DNA at W0 and their impact on virological failure (2 consecutive VL> 50 copies / mL) and on the acquisition of drugs resistance mutations |  | Week 0 | 
| Frequency of grade 3 or more adverse events, adverse effects, drug-modifying adverse events, drug-related adverse events and serious adverse events (SAE) |  | Week 0 to Week 48 | 
| Evolution of T CD4 and CD8 cells count, and CD4/CD8 ratio |  | Week-4 to Week 48 | 
| Evolution of fasting metabolic parameters (total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia) until W0 and W48 |  | Week 0 to Week 48 | 
| Evolution of weight between Week 0 and Week 48 |  | Week 0 and Week 48 | 
| Evolution of inflammation serum parameters | immuno-virological sub-study- (sCD14, sCD163, IP-10, CRPus, IL-6, D-dimers, sTNFR1, sTNFR2) from W0 to W24 and W48 | Week 0 to Week 24 and Week 48 | 
| Evolution of semen viral load at Week 0, Week 24 and Week 48 | Sub-study | Week 0-Week 24 and Week 48 | 
| Description and comparison of plasmatic concentrations of antiretroviral agents between the 2 groups at ON and OFF period |  | Week 0-Week 8-Week 24-Week 48 | 
| Evaluation of the adherence by self-reported questionnaire |  | At Week 0, Week 8, Week 24, Week 36 and Week 48-the evaluation will be done after analysis of all the points | 
| Evolution of the quality of life by self-reported questionnaire |  | Week-4 to Week 48-the evaluation will be done after analysis of all the points | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bitherapy, treatment discontinution, 4 days per week