Clinical trial NCT02157311: 4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV Patients
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV-1
simplification,
treatment discontinuation
virological success
four days a week
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2014-06-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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 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

Primary outcomes:
measure: Capacity to maintain a therapeutic success with 4 days on treatment followed 3 days off treatment
timeFrame: Week 48
Secondary outcomes:
measure: Virological success
timeFrame: Week 48
measure: The time of virological failure occurrence
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: The blips
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: The low viral loads (between 20 - 50 cp/mL)
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: Detected signal on viral quantification
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: Mutations resistance
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: Evaluation CD4, CD8 and CD4/CD8 ratios
timeFrame: Week 0, week 8, week 16, week 24, week 24, week 32, week 40 and week 48
measure: HIV proviral DNA
timeFrame: Week 0, Week 24 and Week 48
measure: Clinical events related to HIV infection
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: Adverse events
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: Interruption or modification of the therapeutic strategy
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: Renal parameters
timeFrame: Week 0, week 8, week 16, week 24, week 32, week 40 and week 48
measure: Inflammation and immune activation
timeFrame: Week 0, week 24 and Week 48
measure: Antiretrovirals Pharmacokinetic
timeFrame: Week 0, week 24 and week 48
measure: Antiretrovirals pharmacokinetic
timeFrame: week 4, week8, week 12, week 24, week 32 and week 48
measure: Quality of life
timeFrame: week 0, week 24 and week 48
measure: Adherence
timeFrame: Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51
measure: Hepatitis parameters
timeFrame: Week 0, week 8, week 16, week 24, week 32, week 40 and week 48
measure: Glucidolipidics parameters
timeFrame: Week 0, week 24 and week 48
Other outcomes:
Locations:
city: Fort-de-france
country: France
facility: Hôpital Meynard
state: Martinique
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Caen
country: France
facility: CHU Côte de Nacre
city: Corbeil Essonnes
country: France
facility: Centre Hospitalier Sud Francilien
city: Dijon
country: France
facility: Hôpital Le Bocage
city: Garches
country: France
facility: Hôpital Raymond Poincaré
city: Kremlin Bicetre
country: France
facility: Hôpital Bicêtre
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital Tenon
city: Suresnes
country: France
facility: Hôpital Foch
city: Toulouse
country: France
facility: Hôpital Purpan
city: Tours
country: France
facility: Hôpital Bretonneau
Study officials:
affiliation: Hôpital Raymond Poincaré
name: Christian PERRONNE, MD-PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Raymond Poincaré
name: Jean-Claude MELCHIOR, MD-PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Raymond Poincaré
name: Pierre DE TRUCHIS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Raymond Poincaré
name: Damien LE DU, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Truchis P, Assoumou L, Landman R, Mathez D, Le Du D, Bellet J, Amat K, Katlama C, Gras G, Bouchaud O, Duracinsky M, Abe E, Alvarez JC, Izopet J, Saillard J, Melchior JC, Leibowitch J, Costagliola D, Girard PM, Perronne C; ANRS 162-4D Study Group. Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial. J Antimicrob Chemother. 2018 Mar 1;73(3):738-747. doi: 10.1093/jac/dkx434.