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

November 5, 2021 updated by: ANRS, Emerging Infectious Diseases

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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%.

Study Type

Interventional

Enrollment (Anticipated)

440

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Argenteuil Cedex, France, 95107
        • Recruiting
        • Centre hospitalier Victor Dupouy/Service d'Hématologie-Unité d'Immunologie
        • Contact:
          • Fabienne CABY
      • Bobigny cedex, France, 93009
        • Recruiting
        • Hôpital Avicenne/Service des Maladies Infectieuses et tropicales
        • Contact:
          • Olivier BOUCHAUD
      • Bordeaux cedex, France, 33075
        • Recruiting
        • Hôpital Saint André/Service HDJ Maladies Infectieuses
        • Contact:
          • Philippe MORLAT
      • Bordeaux cedex, France, 33076
        • Recruiting
        • Hôpital Pellegrin/Service des Maladies Infectieuses et Tropicales
        • Contact:
          • Didier NEAU
      • Caen cedex 9, France, 14033
        • Recruiting
        • Hôpital Côte de Nacre/Service des Maladies Infectieuses
        • Contact:
          • Renaud VERDON
      • Clamart cedex, France, 92141
        • Recruiting
        • Hôpital Antoine Béclère/Service d'Immunologie Clinique et Médecine Interne
        • Contact:
          • Sophie ABGRALL
      • Corbeil-Essonnes cedex, France, 91106
        • Recruiting
        • Centre Hospitalier Sud-Francilien/Service d'Hématologie
        • Contact:
          • Amélie CHABROL
      • Dijon cedex, France, 21079
        • Recruiting
        • Hôpital François Mitterrand/Service des Maladies Infectieuses
        • Contact:
          • Lionel PIROTH
      • Garches, France, 92380
        • Recruiting
        • Hôpital Raymond Poincaré/Service des Maladies Infectieuses
        • Contact:
          • Pierre DE TRUCHIS
      • La Roche sur Yon cedex 9, France, 85925
        • Recruiting
        • CHD de La Roche sur Yon/Service de Médecine Interne
      • Levallois-Perret, France, 92300
        • Recruiting
        • Hôpital Franco-Britannique-Fondation Cognacq-Jay
        • Principal Investigator:
          • Gilles FORCE
      • Limoges, France, 87042
        • Recruiting
        • CHU Dupuytren 1/Service des Maladies Infectieuses et Tropicales
      • Lyon cedex 4, France, 69317
        • Recruiting
        • Hôpital de la Croix Rousse/Service des Maladies Infectieuses
        • Contact:
          • Patrick MIAILHES
      • Marseille cedex 01, France, 13331
        • Recruiting
        • Hôpital Européen/Consultation de Médecine Interne et Maladies Infectieuses
        • Contact:
          • Christina PSOMAS
      • Marseille cedex 9, France, 13274
        • Recruiting
        • Hôpital Sainte Marguerite/Service d'Immuno-Hématologie Clinique
        • Contact:
          • Olivia ZAEGEL-FAUCHER
      • Montpellier cedex 5, France, 34295
        • Recruiting
        • Hôpital Gui de Chauliac/Service des Maladies Infectieuses
        • Contact:
          • Jacques Reynes
      • Nantes cedex 1, France, 44093
        • Recruiting
        • Hôpital de l'Hôtel Dieu/Service des Maladies Infectieuses
        • Contact:
          • Clothilde ALLAVENA
      • Nice cedex 3, France, 06202
        • Recruiting
        • Hôpital de l'Archet/Service des Maladies Infectieuses
        • Contact:
          • Vanessa RIO
      • Paris, France, 75018
        • Recruiting
        • Hôpital Bichat/Service des Maladies Infectieuses
        • Contact:
          • Roland LANDMAN
      • Paris cedex 10, France, 75475
        • Recruiting
        • Hôpital Lariboisière/Service de Médecine Interne
        • Contact:
          • Myriam DIEMER
      • Paris cedex 10, France, 75475
        • Recruiting
        • Hôpital Saint Louis/Service des Maladies Infectieuses
        • Contact:
          • Nathalie DE CASTRO
      • Paris cedex 12, France, 75571
        • Recruiting
        • Hôpital Saint Antoine/Service des Maladies Infectieuses
        • Contact:
          • Karine LACOMBE
      • Paris cedex 13, France, 75651
        • Recruiting
        • Hôpital Pitié-Salpêtrière/Service des Maladies Infectieuses
        • Contact:
          • Christine KATLAMA
      • Paris cedex 15, France, 75743
        • Recruiting
        • Hôpital Necker/Service des Maladies Infectieuses
        • Contact:
          • Claudine DUVIVIER
      • Paris cedex 20, France, 75970
        • Recruiting
        • Hôpital Tenon/Service des Maladies Infectieuses
        • Contact:
          • Gilles PIALOUX
      • Paris cedex 4, France, 75181
        • Recruiting
        • Hôpital Hôtel Dieu/Service d'Immunologie Clinique
        • Contact:
          • Juliette PAVIE
      • Paris cedex 4, France, 75181
        • Recruiting
        • Hôpital Hôtel Dieu/Unité fonctionnelle de Pathologie Infectieuse
        • Contact:
          • Dominique SALMON-CERON
      • Poissy, France, 78300
        • Recruiting
        • Centre hospitalier de Poissy/Service des Maladies Infectieuses
        • Contact:
          • Benoit CAZENAVE
      • Pontoise, France, 95301
        • Recruiting
        • Centre Hospitalier René Dubos/Service de Dermatologie
        • Contact:
          • Laurent BLUM
      • Reims cedex, France, 51092
        • Not yet recruiting
        • Hôpital Robert DEBRE/Service des maladies infectieuses
        • Principal Investigator:
          • Firouzé BANI-SADR
      • Saint Denis cedex 1, France, 93205
        • Recruiting
        • Hôpital Delafontaine/Service des Maladies Infectieuses
        • Contact:
          • Marie-Aude KHUONG-JOSSES
      • Strasbourg Cedex, France, 67091
        • Recruiting
        • Hôpital Civil/Service Le Trait D'union UF 2066
        • Contact:
          • David REY
      • Suresnes, France, 92151
        • Recruiting
        • Hôpital Foch/Service de Médecine Interne
        • Contact:
          • David ZUCMAN
      • Toulouse cedex, France, 31059
        • Recruiting
        • Hôpital Purpan/Service des Maladies Infectieuses
        • Contact:
          • Pierre DELOBEL
      • Tourcoing cedex, France, 59208
        • Recruiting
        • Hôpital Gustave Dron/Service des Maladies Infectieuses
        • Contact:
          • Olivier ROBINEAU
      • Tours, France, 37044
        • Recruiting
        • Hôpital Bretonneau/Service des Maladies Infectieuses
    • Le Coudray
      • Chartres, Le Coudray, France, 28630
        • Recruiting
        • Hôpital Louis Pasteur/Service des Maladies Infectieuses
        • Contact:
          • Juliana DARASTEANU
  • Martinique
      • Fort-de-France, Martinique, 97261
        • Recruiting
        • Hôpital Pierre Zobda-Quitman/Service de Médecine Interne
        • Contact:
          • André CABIE

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with virological failure at Week 48.
Time Frame: 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
Time Frame: Week 48
Week 48
Percentage of participants with at least one episode of "blip"
Time Frame: Week 0 to Week48
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
Time Frame: Week 0 to Week 48
Week 0 to Week 48
Evolution of ultrasensitive viral load and total DNA in the PBMC at W0 and W48
Time Frame: Week 0 and Week 48
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
Time Frame: Week 0 to Week 48
Week 0 to Week 48
Description of selected mutations at the virological failure
Time Frame: Week 0 to Week 48
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
Time Frame: Week 0
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)
Time Frame: Week 0 to Week 48
Week 0 to Week 48
Evolution of T CD4 and CD8 cells count, and CD4/CD8 ratio
Time Frame: Week-4 to Week 48
Week-4 to Week 48
Evolution of fasting metabolic parameters (total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia) until W0 and W48
Time Frame: Week 0 to Week 48
Week 0 to Week 48
Evolution of weight between Week 0 and Week 48
Time Frame: Week 0 and Week 48
Week 0 and Week 48
Evolution of inflammation serum parameters
Time Frame: 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
Week 0 to Week 24 and Week 48
Evolution of semen viral load at Week 0, Week 24 and Week 48
Time Frame: 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
Time Frame: Week 0-Week 8-Week 24-Week 48
Week 0-Week 8-Week 24-Week 48
Evaluation of the adherence by self-reported questionnaire
Time Frame: At Week 0, Week 8, Week 24, Week 36 and Week 48-the evaluation will be done after analysis of all the points
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
Time Frame: Week-4 to Week 48-the evaluation will be done after analysis of all the points
Week-4 to Week 48-the evaluation will be done after analysis of all the points

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANRS, Emerging Infectious Diseases

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Roland LANDMAN, Hopital Bichat

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2021

Primary Completion (Anticipated)

July 1, 2023

Study Completion (Anticipated)

July 1, 2024

Study Registration Dates

First Submitted

April 20, 2021

First Submitted That Met QC Criteria

April 29, 2021

First Posted (Actual)

April 30, 2021

Study Record Updates

Last Update Posted (Actual)

November 8, 2021

Last Update Submitted That Met QC Criteria

November 5, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 177 DUETTO
  • 2020-003951-13 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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