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

NCT02157311 | Completed Phase 3 DMC

• 2 other identifiers: ANRS162-4D2014-000146-29
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 17

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).

Conditions

HIV-1 Infection

Keywords

HIV-1; simplification,; treatment discontinuation; virological success; four days a week

Outcome Measures

Primary Outcomes (1)

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

  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).

  Week 48

Secondary Outcomes (19)

• Virological success

  Week 48

• The time of virological failure occurrence

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

• The blips

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

• The low viral loads (between 20 - 50 cp/mL)

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

• Detected signal on viral quantification

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

Study Arms (1)

Four consecutive days on treatment and 3 days off

EXPERIMENTAL

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

Interventions

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

Also known as: tenofovir,, emtricitabine,, abacavir,, lamivudine,, efavirenz,, rilpivirine,, etravirine,, lopinavir/r,, darunavir/r,, atazanavir/r

Four consecutive days on treatment and 3 days off

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (17)

Hôpital Meynard

Fort-de-france, Martinique, 97261, France

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

CHU Côte de Nacre

Caen, 14033, France

Location

Centre Hospitalier Sud Francilien

Corbeil-Essonnes, 91100, France

Location

Hôpital Le Bocage

Dijon, 21079, France

Location

Hôpital Raymond Poincaré

Garches, 92380, France

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital Gui de Chauliac

Montpellier, 34295, France

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Hôpital Necker

Paris, 75015, France

Location

Hôpital Bichat

Paris, 75018, France

Location

Hôpital Tenon

Paris, 75020, France

Location

Hôpital Foch

Suresnes, 92151, France

Location

Hôpital Purpan

Toulouse, 31059, France

Location

Hôpital Bretonneau

Tours, 37044, France

Location

Related Publications (1)

• 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.

  PMID: 29186458 DERIVED

MeSH Terms

Interventions

Tenofovir; Emtricitabine; abacavir; Lamivudine; efavirenz; Rilpivirine; etravirine; atazanavir, ritonavir drug combination

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Dideoxynucleosides; Nitriles

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2014
• First Posted: June 6, 2014
• Study Start: July 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 27, 2016

Record last verified: 2016-01

Locations

FR (17)