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Completed

NCT Number: NCT02157311

4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV Patients

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).

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Key information

Conditions

HIV-1 Infection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hôpital Meynard, Fort-de-france, Martinique, France

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 :
  • NRTI : tenofovir, emtricitabine, abacavir, lamivudine
  • PI/r : lopinavir/r, darunavir/r or atazanavir/r
  • 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

Treatment and study plan

Four consecutive days on treatment and 3 days off

Drug

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

Primary outcomes

  1. Capacity to maintain a therapeutic success with 4 days on treatment followed 3 days off treatment

    Time frame: Week 48

    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 outcomes

  1. Virological success

    Time frame: Week 48

    The HIV-1 viral load at week 48 must be inferior to 50 copies/mL

  2. 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

    Measure the delay between week 0 and the date of the different virologic failure

  3. The blips

    Time frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51

    Number of blips (viral load detectable on 1 sample) during the study

  4. 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

    Measurement of the low viral loads (between 20 - 50 cop/mL)

  5. 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

    The presence or not of detected signal when no quantification is possible on viral loads

  6. Mutations resistance

    Time frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51

    The profile of new resistance mutations in case of virological failure

  7. 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

    Measurement of the CD4 cell count, CD8 cell count, and CD4/CD8 ratio

  8. HIV proviral DNA

    Time frame: Week 0, Week 24 and Week 48

    The evolution of HIV proviral DNA in the peripheral blood mononuclear cells (PBMC)

  9. 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

    Clinical events related to HIV infection, according to the US CDC classification

  10. Adverse events

    Time frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51

    Collect all clinical and biological adverse events

  11. 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

    Every interruption or modification of the therapeutic strategy for more than 30 days

  12. Renal parameters

    Time frame: Week 0, week 8, week 16, week 24, week 32, week 40 and week 48

    The evolution of creatinin and clearance of creatinin between week 0 and Week 48.

  13. Inflammation and immune activation

    Time frame: Week 0, week 24 and Week 48

    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

  14. Antiretrovirals Pharmacokinetic

    Time frame: Week 0, week 24 and week 48

    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

  15. Antiretrovirals pharmacokinetic

    Time frame: week 4, week8, week 12, week 24, week 32 and week 48

    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

  16. Quality of life

    Time frame: week 0, week 24 and week 48

    selfquestionnary to measure the quality of life (PRO-QOL HIV and felt symptoms )

  17. Adherence

    Time frame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51

    Measurement of treatment adherence (questionnaire, self-survey book, pharmacological measures of antiretroviral drugs, medication event monitoring system)

  18. Hepatitis parameters

    Time frame: Week 0, week 8, week 16, week 24, week 32, week 40 and week 48

    Measurment of AST, SGOT, CGT

  19. Glucidolipidics parameters

    Time frame: Week 0, week 24 and week 48

    Measurement of Glycemia, Triglycerids, total cholesterol, HDL and LDL

Sponsors and collaborators

Lead sponsor

ANRS, Emerging Infectious Diseases

Other Gov

Registry information

Official study 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.

Acronym: ANRS162-4D

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Jun 6, 2014
Registry last updated
Jan 27, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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