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4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV Patients (ANRS162-4D)

This study is ongoing, but not recruiting participants.
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: October 28, 2014
Last verified: October 2014

May 21, 2014
October 28, 2014
July 2014
January 2016   (final data collection date for primary outcome measure)
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).
Same as current
Complete list of historical versions of study NCT02157311 on ClinicalTrials.gov Archive Site
  • 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: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ Designated as safety issue: Yes ]
    Measure the delay between week 0 and the date of the different virologic failure
  • The blips [ Time Frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ 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: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ Designated as safety issue: Yes ]
    Measurement of the low viral loads (between 20 - 50 cop/mL)
  • Detected signal on viral quantification [ Time Frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ Designated as safety issue: Yes ]
    The presence or not of detected signal when no quantification is possible on viral loads
  • Mutations resistance [ Time Frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ 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: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ Designated as safety issue: Yes ]
    Clinical events related to HIV infection, according to the US CDC classification
  • Adverse events [ Time Frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ Designated as safety issue: Yes ]
    Collect all clinical and biological adverse events
  • Interruption or modification of the therapeutic strategy [ Time Frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ 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: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 ] [ 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
  • 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
Not Provided
Not Provided
 
4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV Patients
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.

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).

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

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV-1 Infection
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
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
Intervention: Drug: Four consecutive days on treatment and 3 days off
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
100
January 2016
January 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT02157311
ANRS162-4D, 2014-000146-29
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Not Provided
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
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP