Dual Therapy in HIV Patients in 4 Days a Week Versus 7 Days a Week
- Conditions
- HIV Infections
- Interventions
- Drug: ARV bitherapie
- Registration Number
- NCT04867083
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- Brief Summary
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
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%.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 440
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: 4 days/7 ARV bitherapie 4 days/7 Patients included in this arm will take their ARV treatment 4 consecutive days per week during 48 weeks. Arm 2: 7 days/7 ARV bitherapie Patients included in this arm will take their ARV treatment 7 days per week during 48 weeks
- Primary Outcome Measures
Name Time Method Proportion of patients with virological failure at Week 48. 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
- Secondary Outcome Measures
Name Time Method Proportion of participants with therapeutic success until Week 48 Week 48 Percentage of participants with at least one episode of "blip" Week 0 to Week48 viral load \>50 copies/mL followed by a control value ≤ 50 cp/mL
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 Week 0 and Week 48 immuno-virological sub-study
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 Week 0 to Week 24 and Week 48 immuno-virological sub-study- (sCD14, sCD163, IP-10, CRPus, IL-6, D-dimers, sTNFR1, sTNFR2) from W0 to W24 and W48
Evolution of semen viral load at Week 0, Week 24 and Week 48 Week 0-Week 24 and Week 48 Sub-study
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
Trial Locations
- Locations (38)
Centre hospitalier Victor Dupouy/Service d'Hématologie-Unité d'Immunologie
🇫🇷Argenteuil Cedex, France
Hôpital Louis Pasteur/Service des Maladies Infectieuses
🇫🇷Chartres, Le Coudray, France
Centre hospitalier de Poissy/Service des Maladies Infectieuses
🇫🇷Poissy, France
Hôpital Saint Antoine/Service des Maladies Infectieuses
🇫🇷Paris cedex 12, France
Hôpital Franco-Britannique-Fondation Cognacq-Jay
🇫🇷Levallois-Perret, France
Hôpital Avicenne/Service des Maladies Infectieuses et tropicales
🇫🇷Bobigny cedex, France
Hôpital Saint Louis/Service des Maladies Infectieuses
🇫🇷Paris cedex 10, France
Hôpital François Mitterrand/Service des Maladies Infectieuses
🇫🇷Dijon cedex, France
Hôpital Antoine Béclère/Service d'Immunologie Clinique et Médecine Interne
🇫🇷Clamart cedex, France
Hôpital de l'Hôtel Dieu/Service des Maladies Infectieuses
🇫🇷Nantes cedex 1, France
Centre Hospitalier Sud-Francilien/Service d'Hématologie
🇫🇷Corbeil-Essonnes cedex, France
Hôpital Pellegrin/Service des Maladies Infectieuses et Tropicales
🇫🇷Bordeaux cedex, France
Hôpital Raymond Poincaré/Service des Maladies Infectieuses
🇫🇷Garches, France
Hôpital Gui de Chauliac/Service des Maladies Infectieuses
🇫🇷Montpellier cedex 5, France
Hôpital Côte de Nacre/Service des Maladies Infectieuses
🇫🇷Caen cedex 9, France
CHD de La Roche sur Yon/Service de Médecine Interne
🇫🇷La Roche sur Yon cedex 9, France
Hôpital de la Croix Rousse/Service des Maladies Infectieuses
🇫🇷Lyon cedex 4, France
Hôpital Saint André/Service HDJ Maladies Infectieuses
🇫🇷Bordeaux cedex, France
Hôpital de l'Archet/Service des Maladies Infectieuses
🇫🇷Nice cedex 3, France
CHU Dupuytren 1/Service des Maladies Infectieuses et Tropicales
🇫🇷Limoges, France
Hôpital Européen/Consultation de Médecine Interne et Maladies Infectieuses
🇫🇷Marseille cedex 01, France
Centre Hospitalier René Dubos/Service de Dermatologie
🇫🇷Pontoise, France
Hôpital Bretonneau/Service des Maladies Infectieuses
🇫🇷Tours, France
Hôpital Foch/Service de Médecine Interne
🇫🇷Suresnes, France
Hôpital Pierre Zobda-Quitman/Service de Médecine Interne
🇲🇶Fort-de-France, Martinique
Hôpital Pitié-Salpêtrière/Service des Maladies Infectieuses
🇫🇷Paris cedex 13, France
Hôpital Hôtel Dieu/Service d'Immunologie Clinique
🇫🇷Paris cedex 4, France
Hôpital Sainte Marguerite/Service d'Immuno-Hématologie Clinique
🇫🇷Marseille cedex 9, France
Hôpital Lariboisière/Service de Médecine Interne
🇫🇷Paris cedex 10, France
Hôpital Necker/Service des Maladies Infectieuses
🇫🇷Paris cedex 15, France
Hôpital Tenon/Service des Maladies Infectieuses
🇫🇷Paris cedex 20, France
Hôpital Hôtel Dieu/Unité fonctionnelle de Pathologie Infectieuse
🇫🇷Paris cedex 4, France
Hôpital Bichat/Service des Maladies Infectieuses
🇫🇷Paris, France
Hôpital Robert DEBRE/Service des maladies infectieuses
🇫🇷Reims cedex, France
Hôpital Delafontaine/Service des Maladies Infectieuses
🇫🇷Saint Denis cedex 1, France
Hôpital Civil/Service Le Trait D'union UF 2066
🇫🇷Strasbourg Cedex, France
Hôpital Purpan/Service des Maladies Infectieuses
🇫🇷Toulouse cedex, France
Hôpital Gustave Dron/Service des Maladies Infectieuses
🇫🇷Tourcoing cedex, France