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Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients (QUATUOR)

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ClinicalTrials.gov Identifier: NCT03256422
Recruitment Status : Active, not recruiting
First Posted : August 22, 2017
Last Update Posted : February 5, 2018
Sponsor:
Collaborators:
IMEA Leon M'Ba Foundation
Unit 1136 INSERM, Faculty of medecine, University Pierre and Marie Curie
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Brief Summary:
The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus continuous therapy, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral treatment since 4 months.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Treatment discontinuation Phase 3

Detailed Description:

Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus continuous therapy, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral treatment since 4 months. The non-inferiority margin (delta) is 5%. The randomization will be stratified according to the family of the third antiretroviral agent (II, PI, and NNRTI). A minimum of 200 patients will be included in the integrase inhibitor strata to provide a sufficient power to assess the efficacy of strategy in this population.

At W48, all patients with virological success in the continuous therapy group will switch to the 4/7 days therapy.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Open-label, randomized trial in 2 parallel groups
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Open-label and Multicentric Trial Evaluating the Non-inferiority of Antiretroviral Treatment Taken 4 Consecutive Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients With Controlled Viral Load Under Antiretroviral Therapy
Actual Study Start Date : September 7, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: 4 days / 7
Patients included in this arm will take their ARV treatment 4 consecutive days per week during 98 weeks
Drug: Treatment discontinuation

• Receiving tritherapy. Allowed treatment drugs are :

  1. nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine
  2. protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r
  3. non nucleoside reverse transcriptase inhibitors : efavirenz, rilpivirine ou etravirine
  4. integrase inhibitors : dolutegravir, elvitegravir/cobicistat ou raltegravir

Active Comparator: 7 days / 7
Patients included in this arm will continue their ARV therapy 7 days per weeks during 48 weeks and after W48, they will take their ARV treatment 4 days per week until W98
Drug: Treatment discontinuation

• Receiving tritherapy. Allowed treatment drugs are :

  1. nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine
  2. protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r
  3. non nucleoside reverse transcriptase inhibitors : efavirenz, rilpivirine ou etravirine
  4. integrase inhibitors : dolutegravir, elvitegravir/cobicistat ou raltegravir




Primary Outcome Measures :
  1. Proportion of patients with therapeutic success at Week 48. [ Time Frame: Week 48 ]

    To evaluate after 48 weeks the therapeutic success of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, defined by :

    • absence of virological failure : a measure of the viral load will be done, this measure have to be < 50 cp/mL. If it's > 50 cp/mL, a second measure will be done at 2 to 4 weeks apart. If it's still > 50 cp/mL, it's a virological failure
    • no discontinuation or modification of the study strategy for more than 30 consecutive days.


Secondary Outcome Measures :
  1. Proportion of patients with therapeutic success at Week 96 [ Time Frame: Week 96 ]

    To evaluate after 96 weeks the therapeutic success of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, defined by :

    • absence of virological failure : a measure of the viral load will be done, this measure have to be < 50 cp/mL. If it's > 50 cp/mL, a second measure will be done at 2 to 4 weeks apart. If it's still > 50 cp/mL, it's a virological failure
    • no discontinuation or modification of the study strategy for more than 30 consecutive days.

  2. Virological success [ Time Frame: Week 48 and Week 96 ]
    The HIV-1 viral load at week 48 must be inferior to 50 copies/mL

  3. Number of virological " blips " [ Time Frame: between Week 0 and Week 48, and between Week 0 and Week 96 ]
    viral load > 50 copies/mL followed by a control value ≤ 50 cp/mL

  4. Percentage of patients with a viral load signal detected [ Time Frame: between Week 0 and Week 48 and Week 0 and Week 96 ]
    (subgroup of patients tested with Roche-Taqman, threshold<20 copies/mL)

  5. Proportion of patients with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by next generation sequencing [ Time Frame: Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary) ]
  6. Frequency of minority resistant variants archived in DNA at Week 0 and their impact on virological failure (2 consecutive VL> 50 copies / mL) and on the acquisition of drugs resistance mutations [ Time Frame: Week 0 ]
  7. Evolution of ultra sensitive viral load and total DNA in the peripheral blood mononuclear cells at Week 0, Week 24, Week 48 and Week 96; evolution of viral genotypic sequence between Week 0, Week 48 and Week 96 (subgroup of 120 patients) [ Time Frame: between Week 0, Week 48 and Week 96 ]
    Immuno-viro-pharmacological sub-study of 120 patients

  8. Description of the factors associated with virological rebound (viral load >50 cp/mL). [ Time Frame: Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary) ]
    (viral load >50 cp/mL).

  9. Evolution of T cluster of differentiation 4 and cluster of differentiation 8 cells count, and T cluster of differentiation 4 /cluster of differentiation 8 ratio [ Time Frame: from Week-4 to Week 48 and Week 96 ]
    Measurement of T cluster of differentiation 4 cell count, T cluster of differentiation 8 cell count, and T cluster of differentiation 4 /T cluster of differentiation 8 ratio

  10. Evolution of fasting metabolic parameters [ Time Frame: until Week 48 and Week 96 ]
    Measurement of total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia

  11. Evolution of inflammation and immune activation parameters [ Time Frame: from Week 0 to Week 24 and Week 48 ]
    Measurement of sCD14, sCD163, IP-10, C-reactive protein, interleukin-6 et D-dimerus, soluble TNF receptor 1, soluble TNF receptor 2 Immuno-viro-Pharmacological Sub-study in 120 patients

  12. HIV RNA viral load in semen [ Time Frame: Week 0, Week 24 and Week 48 ]
    Sperm sub-study (120 patients)

  13. Residual plasmatic concentrations of the third antiretroviral agent [ Time Frame: Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 ]
    Measurement of the third antiretroviral agent plasmatic concentration (protease inhibitors or non-nucleoside reverse transcriptase inhibitors or integrase inhibitors)

  14. Residual plasmatic concentrations of tenofovir (TDF or TAF) [ Time Frame: Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 ]
    Measurement of tenofovir plasmatic concentration

  15. Residual intracellular concentrations of the third antiretroviral agents [ Time Frame: Week 0, Week 24 and Week 48 ]
    Immuno-viro-Pharmacological sub-study (120 patients) Measurement of the third antiretroviral agent intracellular concentration (protease inhibitors or non-nucleoside reverse transcriptase inhibitors or integrase inhibitors)

  16. Treatment adherence [ Time Frame: Week 0, Week 12, Week 24, Week 36, Week 48, Week 72,and Week 96 ]
    Evaluation by a self-reported questionnaire

  17. Quality of life [ Time Frame: Week-4, Week 0, Week 48 and Week 96 ]
    Evaluation by a self-reported questionnaire

  18. Patient satisfaction [ Time Frame: Week 0, Week 12, Week 48 and Week 96 ]
    Evaluation by a self-reported questionnaire

  19. Pharmaco-economic aspects of the strategy [ Time Frame: Between Week 0 and Week 98 ]
    Assessment and comparison of cost essay between each arm.

  20. Median time to virologic failure [ Time Frame: Between week 0 and 98 ]
    Measure the delay between week 0 and the date of different virologic failure

  21. 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: Between Week 0 and Week 98 ]
    according to the sponsor's grading scale



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection, coinfection HIV-1/HIV-2 possible
  • Age≥18 years old
  • Current therapy unchanged for the last 4 months
  • Receiving tritherapy with 2 nucleoside reverse transcriptase inhibitor+protease inhibitors or 2 nucleoside reverse transcriptase inhibitor+non-nucleoside reverse transcriptase inhibitors or 2 nucleoside reverse transcriptase inhibitor+integrase inhibitors.

Allowed treatment drugs are :

1. nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine 2. protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r 3. Non nucleoside reverse transcriptase inhibitors : efavirenz, rilpivirine ou etravirine 4. integrase inhibitors : dolutegravir, elvitegravir/cobicistat ou raltegravir

  • Viruses susceptible to all antiretroviral drugs present in the ongoing tritherapy (AC11-ANRS algorithm).

    1. If a genotype is available in the patient medical history; viruses must be susceptible to all ongoing antiretroviral drugs
    2. If no RNA genotype available, a genotype will be performed on DNA at screening and will not have to show any resistance to the ongoing antiretroviral drugs
  • Viral load (VL) < 50 cp/mL in the past year, with at least 3 VL measurements including screening; only one episode of viral blip < 200 copies/mL is authorized in the last year
  • CD4 T cells > 250/mm3 at the screening visit
  • Estimated glomerular filtration rate > 60 mL/min (Chronic Kidney Disease - Epidemiology Collaboration method)
  • Transaminases : aspartate aminotransférase et alanine aminotransférase < 3N
  • Haemoglobin > 10 g/dL
  • Platelets > 100 000/mm3
  • For women of childbearing age, negative pregnancy test at screening; agree to use mechanical contraception during the study
  • Social security system coverage
  • Informed consent form signed by patient and investigator

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 98 weeks
  • Concomitant treatment using interferon, interleukins, any other immune-therapy or chemotherapy, antivitaminK for patients on ARVT using a 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03256422


  Show 63 Study Locations
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
IMEA Leon M'Ba Foundation
Unit 1136 INSERM, Faculty of medecine, University Pierre and Marie Curie
Investigators
Principal Investigator: Pierre De Truchis, MD Hôpital Raymond Poincaré

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT03256422     History of Changes
Other Study ID Numbers: ANRS 170 - QUATUOR
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: February 5, 2018
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
Controlled, virological and therapeutic success, treatment discontinution, 4 days per week

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases