Clinical trial NCT04867083: Dual Therapy in HIV Patients in 4 Days a Week Versus 7 Days a Week
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HIV Infections
Keywords: bitherapy
treatment discontinution
4 days per week
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2021-04-30
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, multicenter, prospective, randomized trial in 2 parallel groups
Primary purpose: TREATMENT

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%.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with virological failure at Week 48.
timeFrame: Week 48
Secondary outcomes:
measure: Proportion of participants with therapeutic success until Week 48
timeFrame: Week 48
measure: Percentage of participants with at least one episode of "blip"
timeFrame: Week 0 to Week48
measure: Percentage of participants with a viral load signal detected
timeFrame: Week 0 to Week 48
measure: Evolution of ultrasensitive viral load and total DNA in the PBMC at W0 and W48
timeFrame: Week 0 and Week 48
measure: Proportion of participants with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by NGS
timeFrame: Week 0 to Week 48
measure: Description of selected mutations at the virological failure
timeFrame: Week 0 to Week 48
measure: 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
timeFrame: Week 0
measure: Frequency of grade 3 or more adverse events, adverse effects, drug-modifying adverse events, drug-related adverse events and serious adverse events (SAE)
timeFrame: Week 0 to Week 48
measure: Evolution of T CD4 and CD8 cells count, and CD4/CD8 ratio
timeFrame: Week-4 to Week 48
measure: Evolution of fasting metabolic parameters (total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia) until W0 and W48
timeFrame: Week 0 to Week 48
measure: Evolution of weight between Week 0 and Week 48
timeFrame: Week 0 and Week 48
measure: Evolution of inflammation serum parameters
timeFrame: Week 0 to Week 24 and Week 48
measure: Evolution of semen viral load at Week 0, Week 24 and Week 48
timeFrame: Week 0-Week 24 and Week 48
measure: Description and comparison of plasmatic concentrations of antiretroviral agents between the 2 groups at ON and OFF period
timeFrame: Week 0-Week 8-Week 24-Week 48
measure: Evaluation of the adherence by self-reported questionnaire
timeFrame: At Week 0, Week 8, Week 24, Week 36 and Week 48-the evaluation will be done after analysis of all the points
measure: Evolution of the quality of life by self-reported questionnaire
timeFrame: Week-4 to Week 48-the evaluation will be done after analysis of all the points
Other outcomes:
Locations:
city: Chartres
country: France
facility: Hôpital Louis Pasteur/Service des Maladies Infectieuses
state: Le Coudray
city: Argenteuil Cedex
country: France
facility: Centre hospitalier Victor Dupouy/Service d'Hématologie-Unité d'Immunologie
city: Bobigny cedex
country: France
facility: Hôpital Avicenne/Service des Maladies Infectieuses et tropicales
city: Bordeaux cedex
country: France
facility: Hôpital Saint André/Service HDJ Maladies Infectieuses
city: Bordeaux cedex
country: France
facility: Hôpital Pellegrin/Service des Maladies Infectieuses et Tropicales
city: Caen cedex 9
country: France
facility: Hôpital Côte de Nacre/Service des Maladies Infectieuses
city: Clamart cedex
country: France
facility: Hôpital Antoine Béclère/Service d'Immunologie Clinique et Médecine Interne
city: Corbeil-Essonnes cedex
country: France
facility: Centre Hospitalier Sud-Francilien/Service d'Hématologie
city: Dijon cedex
country: France
facility: Hôpital François Mitterrand/Service des Maladies Infectieuses
city: Garches
country: France
facility: Hôpital Raymond Poincaré/Service des Maladies Infectieuses
city: La Roche sur Yon cedex 9
country: France
facility: CHD de La Roche sur Yon/Service de Médecine Interne
city: Levallois-Perret
country: France
facility: Hôpital Franco-Britannique-Fondation Cognacq-Jay
city: Limoges
country: France
facility: CHU Dupuytren 1/Service des Maladies Infectieuses et Tropicales
city: Lyon cedex 4
country: France
facility: Hôpital de la Croix Rousse/Service des Maladies Infectieuses
city: Marseille cedex 01
country: France
facility: Hôpital Européen/Consultation de Médecine Interne et Maladies Infectieuses
city: Marseille cedex 9
country: France
facility: Hôpital Sainte Marguerite/Service d'Immuno-Hématologie Clinique
city: Montpellier cedex 5
country: France
facility: Hôpital Gui de Chauliac/Service des Maladies Infectieuses
city: Nantes cedex 1
country: France
facility: Hôpital de l'Hôtel Dieu/Service des Maladies Infectieuses
city: Nice cedex 3
country: France
facility: Hôpital de l'Archet/Service des Maladies Infectieuses
city: Paris cedex 10
country: France
facility: Hôpital Lariboisière/Service de Médecine Interne
city: Paris cedex 10
country: France
facility: Hôpital Saint Louis/Service des Maladies Infectieuses
city: Paris cedex 12
country: France
facility: Hôpital Saint Antoine/Service des Maladies Infectieuses
city: Paris cedex 13
country: France
facility: Hôpital Pitié-Salpêtrière/Service des Maladies Infectieuses
city: Paris cedex 15
country: France
facility: Hôpital Necker/Service des Maladies Infectieuses
city: Paris cedex 20
country: France
facility: Hôpital Tenon/Service des Maladies Infectieuses
city: Paris cedex 4
country: France
facility: Hôpital Hôtel Dieu/Service d'Immunologie Clinique
city: Paris cedex 4
country: France
facility: Hôpital Hôtel Dieu/Unité fonctionnelle de Pathologie Infectieuse
city: Paris
country: France
facility: Hôpital Bichat/Service des Maladies Infectieuses
city: Poissy
country: France
facility: Centre hospitalier de Poissy/Service des Maladies Infectieuses
city: Pontoise
country: France
facility: Centre Hospitalier René Dubos/Service de Dermatologie
city: Reims cedex
country: France
facility: Hôpital Robert DEBRE/Service des maladies infectieuses
city: Saint Denis cedex 1
country: France
facility: Hôpital Delafontaine/Service des Maladies Infectieuses
city: Strasbourg Cedex
country: France
facility: Hôpital Civil/Service Le Trait D'union UF 2066
city: Suresnes
country: France
facility: Hôpital Foch/Service de Médecine Interne
city: Toulouse cedex
country: France
facility: Hôpital Purpan/Service des Maladies Infectieuses
city: Tourcoing cedex
country: France
facility: Hôpital Gustave Dron/Service des Maladies Infectieuses
city: Tours
country: France
facility: Hôpital Bretonneau/Service des Maladies Infectieuses
city: Fort-de-France
country: Martinique
facility: Hôpital Pierre Zobda-Quitman/Service de Médecine Interne
Study officials:
affiliation: Hôpital BICHAT
name: Roland LANDMAN
role: PRINCIPAL_INVESTIGATOR
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