4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV Patients (ANRS 162-4D)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
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)
ClinicalTrials.gov Identifier:
NCT02157311
First received: May 21, 2014
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

Evaluate after 48 weeks, the capacity of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, in HIV-1 treated patients with undetectable viral load for at least 12 months and continuous antiretroviral regimen unchanged for at least 4 months, to maintain a therapeutic success defined by the absence of virological failure (2 consecutive viral loads > 50 cp/mL) and the absence of interruption of therapeutic strategy (interruption or change of the " 4 days on / 3 days off " strategy for a time longer than 30 consecutive days).


Condition Intervention Phase
HIV-1 Infection
Drug: Four consecutive days on treatment and 3 days off
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Capacity of a Weekly Strategy of 4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV-1 Infected Patients With Undetectable Viral Load for at Least 12 Months, to Maintain a Virological Success With This Intermittent Maintenance Therapy After a Successful Continuous Induction Therapy.

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Capacity to maintain a therapeutic success with 4 days on treatment followed 3 days off treatment [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    To evaluate after 48 weeks, the capacity of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, in HIV-1 treated patients with undetectable viral load for at least 12 months and continuous antiretroviral regimen unchanged for at least 4 months, to maintain a therapeutic success defined by the absence of virological failure (2 consecutive viral loads > 50 cp/mL) and the absence of interruption of therapeutic strategy (interruption or change of the " 4 days on / 3 days off " strategy for a time longer than 30 consecutive days).


Secondary Outcome Measures:
  • Virological success [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    The HIV-1 viral load at week 48 must be inferior to 50 copies/mL

  • The time of virological failure occurrence [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    Measure the delay between week 0 and the date of the different virologic failure

  • The blips [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    Number of blips (viral load detectable on 1 sample) during the study

  • The low viral loads (between 20 - 50 cp/mL) [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    Measurement of the low viral loads (between 20 - 50 cop/mL)

  • Detected signal on viral quantification [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    The presence or not of detected signal when no quantification is possible on viral loads

  • Mutations resistance [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    The profile of new resistance mutations in case of virological failure

  • Evaluation CD4, CD8 and CD4/CD8 ratios [ Time Frame: Week 0, week 8, week 16, week 24, week 24, week 32, week 40 and week 48 ] [ Designated as safety issue: No ]
    Measurement of the CD4 cell count, CD8 cell count, and CD4/CD8 ratio

  • HIV proviral DNA [ Time Frame: Week 0, Week 24 and Week 48 ] [ Designated as safety issue: No ]
    The evolution of HIV proviral DNA in the peripheral blood mononuclear cells (PBMC)

  • Clinical events related to HIV infection [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    Clinical events related to HIV infection, according to the US CDC classification

  • Adverse events [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    Collect all clinical and biological adverse events

  • Interruption or modification of the therapeutic strategy [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: Yes ]
    Every interruption or modification of the therapeutic strategy for more than 30 days

  • Renal parameters [ Time Frame: Week 0, week 8, week 16, week 24, week 32, week 40 and week 48 ] [ Designated as safety issue: Yes ]
    The evolution of creatinin and clearance of creatinin between week 0 and Week 48.

  • Inflammation and immune activation [ Time Frame: Week 0, week 24 and Week 48 ] [ Designated as safety issue: No ]

    The evolution of inflammation and immune activation parameters (IL-6, CRP-US, CD14s, IP-10 and MIG-1).

    The measurement will be done at the end of the study in a central lab on the biobank


  • Antiretrovirals Pharmacokinetic [ Time Frame: Week 0, week 24 and week 48 ] [ Designated as safety issue: No ]
    The evolution of pharmacokinetic parameters, for protease inhibitors (lopinavir, darunavir or atazanavir) or non-nucleoside reverse transcriptase inhibitors (efavirensz, etravirine or rilpivirine) The measurment will be done on the sample bank at the end of the study in a central lab

  • Antiretrovirals pharmacokinetic [ Time Frame: week 4, week8, week 12, week 24, week 32 and week 48 ] [ Designated as safety issue: Yes ]

    Measurment of Residual plasmatic concentrations of protease inhibitors (lopinavir/r - darunavir/r - atazanavir/r ) or non-nucleoside reverse transcriptase inhibitors (efavirenz or rilpivirine or etravirine), at the end of the 3-days off, from Day 0 to week 48.

    The measurment will be done on the sample bank at the end of the study in a central lab


  • Quality of life [ Time Frame: week 0, week 24 and week 48 ] [ Designated as safety issue: No ]
    selfquestionnary to measure the quality of life (PRO-QOL HIV and felt symptoms )

  • Adherence [ Time Frame: J0, W4, W8, W12, W16, W24, W32, W40, W48, W51 ] [ Designated as safety issue: No ]
    Measurement of treatment adherence (questionnaire, self-survey book, pharmacological measures of antiretroviral drugs, medication event monitoring system)

  • Hepatitis parameters [ Time Frame: Week 0, week 8, week 16, week 24, week 32, week 40 and week 48 ] [ Designated as safety issue: No ]
    Measurment of AST, SGOT, CGT

  • Glucidolipidics parameters [ Time Frame: Week 0, week 24 and week 48 ] [ Designated as safety issue: No ]
    Measurement of Glycemia, Triglycerids, total cholesterol, HDL and LDL


Estimated Enrollment: 100
Study Start Date: June 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Four consecutive days on treatment and 3 days off
All patients will take a combination of three HIV treatment with a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment
Drug: Four consecutive days on treatment and 3 days off
All patients will take a combination of three of these treatment with a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment
Other Names:
  • tenofovir,
  • emtricitabine,
  • abacavir,
  • lamivudine,
  • efavirenz,
  • rilpivirine,
  • etravirine,
  • lopinavir/r,
  • darunavir/r,
  • atazanavir/r

Detailed Description:

Methods:

Open-label, multicentric, prospective, non-randomized, non-controlled trial to evaluate at 48 weeks, the capacity of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, in HIV-1 treated patients with undetectable viral load for at least 12 months and continuous antiretroviral regimen unchanged for at least 4 months, to maintain a therapeutic success defined by the absence of virological failure (2 consecutive viral loads > 50 cp/mL) and the absence of interruption of therapeutic strategy (interruption or change of the " 4 days on / 3 days off " strategy for a time longer than 30 consecutive days).

Allocation: Non-randomized Endpoint Classification: Safety/Efficacy Study Primary Purpose: Treatment

Enrollment: 100 patients

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • • HIV-1 documented infection

    • Age 18 years or older
    • HIV-1 viral load always ≤ 50 cp/mL for at least 12 months (with a minimum of 3 measures in the last 12 months, including screening)
    • CD4+ lymphocytes count > 250/mm3, for at least 6 months
    • Treatment with a stable regimen for at least 4 months prior to screening, containing 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTI) combined with, either 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), or 1 ritonavir-boosted protease inhibitor (PI/r). The list of accepted antiretroviral drugs is limited to :

      1. NRTI : tenofovir, emtricitabine, abacavir, lamivudine
      2. PI/r : lopinavir/r, darunavir/r or atazanavir/r
      3. NNRTI : efavirenz, rilpivirine or etravirine.
    • Exclusive antiretroviral 3 drug-therapy (no 4 drug-therapy)
    • A least one genotypic resistance test available (reverse transcriptase and/or protease amino acid sequence, according to on-going antiretroviral drugs) ; on each genotypic resistance test(s) available in medical history, susceptibility to every on-going antiretroviral drugs must be demonstrated
    • Clearance of the creatinine > 60 mL/min (MDRD)
    • ASAT and ALAT < 3 ULN
    • Hemoglobin > 10 g/dl
    • Platelets count > 100 000/mm3
    • Negative pregnancy test for potential child-bearing women and mechanical contraception for sexual intercourses
    • Patient living in France and affiliated to a social security system
    • Written informed consent

Exclusion Criteria:

  • • HIV-2 infection

    • HBV infection (positive HBs antigen) or isolated positive HBc antibody
    • HCV infection requiring specific treatment during the 51 weeks of the trial
    • At least one known resistance to one of on-going antiretroviral drugs
    • Exclusive antiretroviral 3 drug-therapy (no 4 drug-therapy)
    • No genotypic resistance test available
    • On-going either interferon, interleukin treatment, or every immuno- / chemo-therapy
    • Progressive opportunistic infection, on-going treatment for opportunistic infection or tuberculosis
    • Patient with irregular follow-up or with treatment adherence problems
    • Any condition (alcohol, drug abuse…) compromising treatment adherence, treatment safety, and/or study adherence
    • Progressive neurological disorders (meningitis, encephalitis, myelitis…) related to HIV infection or not
    • Medical history of severe neuropsychiatric disorder, with insufficient treatment efficacy
    • Subject under legal guardianship or incapacitation
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02157311

Contacts
Contact: Karine AMAT, MS +33.1.40.25.63.52 karine.amat@hotmail.fr
Contact: Aïda BENALYCHERIF, MS +33.1.40.25.63.65 aida.benalycherif@gmail.com

Locations
France
Hôpital Meynard Not yet recruiting
Fort-de-france, Martinique, France, 97261
Contact: André CABIE, MD-PHD    +33.5.96.55.23.08    andre.cabie@chu-fortdefrance.fr   
Contact: Christophe CERLAND    +33.5.96.55.96.73    Christophe.Cerland@chu-fortdefrance.fr   
Principal Investigator: André CABIE, MD-PHD         
Sub-Investigator: Sylvie ABEL, MD         
Sub-Investigator: Sandrine PIERRE-FRANCOIS, MD         
Hôpital Avicenne Not yet recruiting
Bobigny, France, 93000
Contact: Olivier BOUCHAUD, MD-PHD    +33.1.48.95.54.21    olivier.bouchau@avc.aphp.fr   
Contact: Patricia HONORE    +33.1.48.95.51.46    patricia.honore@avc.aphp.fr   
Principal Investigator: Olivier BOUCHAUD, MD-PHD         
CHU Côte de Nacre Not yet recruiting
Caen, France, 14033
Contact: Renaud VERDON, MD-PHD    +33.2.31.06.47.14    verdon-r@chu-caen.fr   
Contact: Pascale GOUBIN    +33.2.31.06.50.87    goubin-p@chu-caen.fr   
Principal Investigator: Renaud VERDON, MD-PHD         
Centre Hospitalier Sud Francilien Not yet recruiting
Corbeil Essonnes, France, 91100
Contact: Amélie CHABROL, MD    +33.1.61.69.31.78    amelie.chabrol@ch-sud-francilien.fr   
Principal Investigator: Amélie CHABROL, MD         
Hôpital Le Bocage Not yet recruiting
Dijon, France, 21079
Contact: Lionel PIROTH, MD-PHD    +33.3.80.29.36.31    lionel.piroth@chu-dijon.fr   
Contact: Sandrine GOHIER    +33.3.80.29.36.31    sandrine.gohier@chu-dijon.fr   
Principal Investigator: Lionel PIROTH, MD-PHD         
Hôpital Raymond Poincaré Not yet recruiting
Garches, France, 92380
Contact: Pierre DE TRUCHIS, MD    +33.1.47.10.77.72    p.de-truchis@rpc.aphp.fr   
Contact: Huguette BERTHE    +33.1.47.10.46.65    huguette.berthe@rpc.aphp.fr   
Principal Investigator: Pierre DE TRUCHIS, MD         
Sub-Investigator: Damien LE DU, MD         
Sub-Investigator: Christian PERRONNE, MD-PHD         
Sub-Investigator: Jean-Claude MELCHIOR, MD-PHD         
Hôpital Bicêtre Not yet recruiting
Kremlin Bicetre, France, 94275
Contact: Olivier SEGERAL, MD    +33.1.45.21.2891    olivier.segeral@bct.aphp.fr   
Contact: Marie-Josée DULUCQ    +33.1.45.21.35.32    marie-josee.dulucq@bct.aphp.fr   
Principal Investigator: Olivier SEGERAL, MD         
Hôpital Gui de Chauliac Not yet recruiting
Montpellier, France, 34295
Contact: Jacques REYNES, MD-PHD    +33.4.67.33.72.20    j-reynes@chu-montpellier.fr   
Principal Investigator: Jacques REYNES, MD-PHD         
Hôpital Tenon Not yet recruiting
Paris, France, 75020
Contact: Gilles PIALOUX, MD-PHD    +33.1.56.01.74.36    gilles.pialoux@tnn.aphp.fr   
Contact: Valérie BERREBI    +33.1.56.01.74.36    vakerie.berrebi@tnn.aphp.fr   
Principal Investigator: Gilles PIALOUX, MD-PHD         
Hôpital Saint-Antoine Not yet recruiting
Paris, France, 75012
Contact: Pierre-Marie GIRARD, MD-PHD    +33.1.49.28.24.38    pierre-marie.girard@sat.aphp.fr   
Contact: Michèle PAUCHARD    +33.49.28.24.86    michele.pauchard@sat.aphp.fr   
Principal Investigator: Pierre-Marie GIRARD, MD-PHD         
Sub-Investigator: Benedicte LEFEBVRE, MD         
Sub-Investigator: Diane BOLLENS, MD         
Sub-Investigator: Zineb OUAZENE, MD         
Sub-Investigator: Nadia VALIN, MD         
Hôpital Bichat Not yet recruiting
Paris, France, 75018
Contact: Patrick YENI, MD-PHD    +33.1.40.25.70.57    patrick.yeni@bch.aphp.fr   
Contact: Françoise LOUBNI    +33.1.40.25.70.57    francoise.loubni@bch.aphp.fr   
Principal Investigator: Patrick YENI, MD-PHD         
Sub-Investigator: Yazdan YAZDANPANAH, MD-PHD         
Sub-Investigator: Emmanuelle PAPOT, MD         
Sub-Investigator: Roland LANDMAN, MD         
Hôpital Necker Not yet recruiting
Paris, France, 75015
Contact: Claudine DUVIVIER, MD    +33.1.42.19.27.19    duvivier@nck.aphp.fr   
Contact: Fatima TOUAM    +33.1.42.19.27.19    fatima.touam@nck.aphp.fr   
Principal Investigator: Claudine DUVIVIER, MD         
Hôpital Européen Georges Pompidou Not yet recruiting
Paris, France, 75015
Contact: Laurence WEISS, MD-PHD    +33.1.56.09.32.99    laurence.weiss@egp.aphp.fr   
Contact: Lio COLLIAS, PHD    +33.1.56.09.33.03    lio.collias@egp.aphp.fr   
Principal Investigator: Laurence LW WEISS, MD-PHD         
Sub-Investigator: Lio COLLIAS, MD         
Hôpital Pitié-Salpêtrière Not yet recruiting
Paris, France, 75013
Contact: Christine KATLAMA, MD-PHD    +33.1.42.16.01.59    christine.katlama@psl.aphp.fr   
Contact: Patricia BOURSE    +33.1.42.16.02.93    patricia.bourse@psl.aphp.fr   
Principal Investigator: Christine KATLAMA, MD-PHD         
Hôpital Foch Not yet recruiting
Suresnes, France, 92151
Contact: David ZUCMAN, MD    +33.1.46.25.2.93    d.zucman@hopital-foch.org   
Contact: Dominique BORNAREL    +33.1.46.25.28.01    d.bornarel@hopital-foch.org   
Principal Investigator: David ZUCMAN, MD         
Sub-Investigator: Catherine MAJHERLOC, MD         
Hôpital Purpan Not yet recruiting
Toulouse, France, 31059
Contact: Pierre DELOBEL, MD    +33.5.61.77.75.08    delobel.p@chu-toulouse.fr   
Principal Investigator: Pierre DELOBEL, MD         
Hôpital Bretonneau Not yet recruiting
Tours, France, 37044
Contact: Louis BERNARD, MD-PHD    +33.2.47.47.37.34    l.bernard@chu-tours.fr   
Contact: Eva AOUSTIN    +33.2.47.47.86.22 ext 70143    e.aoustin@chu-tours.fr   
Principal Investigator: Louis BERNARD, MD-PHD         
Sub-Investigator: Guillaume GRAS, MD         
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Christian PERRONNE, MD-PHD Hôpital Raymond Poincaré
Principal Investigator: Jean-Claude MELCHIOR, MD-PHD Hôpital Raymond Poincaré
Principal Investigator: Pierre DE TRUCHIS, MD Hôpital Raymond Poincaré
Principal Investigator: Damien LE DU, MD Hôpital Raymond Poincaré
  More Information

No publications provided

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: NCT02157311     History of Changes
Other Study ID Numbers: ANRS162-4D, 2014-000146-29
Study First Received: May 21, 2014
Last Updated: June 2, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV-1
simplification,
treatment discontinuation
virological success
four days a 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
Emtricitabine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014