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

ANRS, Emerging Infectious Diseases

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: Four consecutive days on treatment and 3 days off

Study type: Interventional

Funder types: Other

Identifiers

NCT02157311

ANRS162-4D

2014-000146-29 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Four consecutive days on treatment and 3 days off

Experimental group

Description:

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

Treatment:

Drug: Four consecutive days on treatment and 3 days off