Study of Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir in HIV-infected Antiretroviral naïve Subjects

NCT ID: NCT01066962

Last Updated: 2013-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2013-10-31

Brief Summary

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The triple therapy darunavir/r + tenofovir/emtricitabine is likely to become a relevant first-line treatment option in the years to come. The dual combination of boosted darunavir + raltegravir is an innovative treatment option that combines two potent new antiretroviral drugs, one of which belongs to a new drug class (integrase inhibitor). The expected efficacy profile of this combination is promising. Moreover, this combination might have a better tolerance profile and has the advantage of sparing the NRTI class.

In the context of tenofovir/emtricitabine currently being a reference backbone in first-line antiretroviral regimens, we hypothesise that, in combination with darunavir/r, raltegravir may be an alternative option if its efficacy is non-inferior to tenofovir/emtricitabine.

Detailed Description

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Conditions

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HIV Infections

Keywords

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HIV-infected antiretroviral naïve subjects

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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darunavir/r + tenofovir/emtricitabine

Group Type ACTIVE_COMPARATOR

darunavir/r QD + tenofovir/emtricitabine QD (fixed dose combination)

Intervention Type DRUG

darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD)

ritonavir 100 mg, 1 tablet once daily (QD)

tenofovir/emtricitabine 245/200 mg, fixed dose combination, 1 tablet once daily (QD)

darunavir/r + raltegravir

Group Type EXPERIMENTAL

darunavir/ritonavir QD + raltegravir BID

Intervention Type DRUG

darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD)

ritonavir 100 mg, 1 tablet once daily (QD)

raltegravir 400 mg, 1 tablet twice daily (BID)

Interventions

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darunavir/ritonavir QD + raltegravir BID

darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD)

ritonavir 100 mg, 1 tablet once daily (QD)

raltegravir 400 mg, 1 tablet twice daily (BID)

Intervention Type DRUG

darunavir/r QD + tenofovir/emtricitabine QD (fixed dose combination)

darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD)

ritonavir 100 mg, 1 tablet once daily (QD)

tenofovir/emtricitabine 245/200 mg, fixed dose combination, 1 tablet once daily (QD)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient with confirmed HIV infection
* Age ≥ 18 years
* Written informed consent
* Male patient or non-pregnant, non-lactating female
* No previous treatment with any antiretroviral drugs
* HIV-1 RNA \> 1000 copies/ml
* Indication to start an antiretroviral treatment as long as subject has also a CD4 cell count ≤ 500/mm3 either at screening or on a sample taken within 3 months before screening
* No major IAS-USA mutations on genotypic testing at the screening visit or on any historical genotype, if available


* Woman without effective contraception method (recommended contraception during the trial is mechanical + a second method other than an oral contraceptive)
* Pregnant or breastfeeding woman
* Woman expecting to conceive during the study
* HIV-2 co-infection
* Creatinine clearance \< 60 ml/mn (Cockcroft \& Gault equation), alkaline phosphatase, ASAT, or ALAT ≥ 5 ULN
* Patient with significant impairment of hepatic function, defined as serum albumin \< 2.8 g/dl or INR \> 1.7 or presence of ascites, in the absence of another explanation for the abnormal finding
* CD4 \> 500/mm3 at screening, except in case of symptomatic HIV disease (defined by conditions qualifying for CDC category B or C) or CD4 ≤ 500/mm3 on a sample taken within 3 months before screening.
* Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or protease inhibitors on genotypic testing at screening
* Mycobacteriosis under treatment
* Malignancy requiring chemotherapy or radiotherapy
* Positive HBs Ag
* HCV infection for which specific treatment is ongoing or planned during the first year on trial treatment
* Known hypersensitivity to one of the trial drugs or its excipients
* Contraindicated concomitant treatment
* Anticipated non-compliance with the protocol
* Participation in another clinical trial with an on-going exclusion period at screening
* Subject under legal guardianship or incapacitation
* Subject, who in the opinion of the investigator, is unable to complete the study period
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NEAT - European AIDS Treatment Network

OTHER

Sponsor Role collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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François Raffi, Professor

Role: STUDY_CHAIR

Nantes University Hospital

Locations

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Allgemeines Krankenhaus der Stadt Wien

Vienna, , Austria

Site Status

Otto Wagner Spital mit Pflegezentrum

Vienna, , Austria

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ITZ Antwerpen

Antwerp, , Belgium

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CHU Saint Pierre

Brussels, , Belgium

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UZ Gent

Ghent, , Belgium

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Rigshospitalet

Copenhagen, , Denmark

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Hvidovre Hospital

Hvidovre, , Denmark

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Hôpital Pellegrin

Bordeaux, , France

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Hôpital Saint André

Bordeaux, , France

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Hôpital Henri Mondor

Créteil, , France

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Hôpital du Bocage

Dijon, , France

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Hôpital Pierre Zobda-Quitman

Fort de France, , France

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CHD de la Roche sur Yon

La Roche-sur-Yon, , France

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Hôpital Bicêtre

Le Kremlin-Bicêtre, , France

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Hôpital Gui de Chauliac

Montpellier, , France

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Hôpital de l'Hôtel Dieu

Nantes, , France

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Hôpital Bichat

Paris, , France

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Hôpital Européen Georges Pompidou (HEGP)

Paris, , France

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Hôpital La Pitié Salpétrière

Paris, , France

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Hôpital Saint Antoine

Paris, , France

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Hôpital Saint Louis

Paris, , France

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Hôpital Pontchaillou

Rennes, , France

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Hôpital Foch

Suresnes, , France

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Hôpital Purpan

Toulouse, , France

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Hôpital Gustave Dron

Tourcoing, , France

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Gemeinschaftspraxis Jessen-Jessen-Stein

Berlin, , Germany

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Med. Universitätsklinik I

Bonn, , Germany

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Universitätsklinik Köln

Cologne, , Germany

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Universitätsklinikum Essen

Essen, , Germany

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Klinikum der Johann Wolfgang Goethe Universität

Frankfurt, , Germany

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Asklepios-Klinik St. Georg

Hamburg, , Germany

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ICH study centre

Hamburg, , Germany

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Medizinische Hochschule Hannover

Hanover, , Germany

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Attikon University Hospital

Athens, , Greece

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Evaggelismos General Hospital

Athens, , Greece

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Laikon General Hospital

Athens, , Greece

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Saint Laszlo Hospital

Budapest, , Hungary

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Mater Misericordiae

Dublin, , Ireland

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St James's Hospital

Dublin, , Ireland

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University of Brescia

Brescia, , Italy

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Ospedale Santa Maria Annunziata

Florence, , Italy

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Fondazione Centro San Raffaele del Monte Tabor

Milan, , Italy

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San Paolo Hospital

Milan, , Italy

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Luigi Sacco Hospital

Milan, , Italy

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Istituto Naziona e per le Malattie "Lazzaro Spallanzani"

Rome, , Italy

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Sapienza Universita di Roma

Rome, , Italy

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Torvergata University

Rome, , Italy

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Ospedale "Amedeo di Savoia"

Turin, , Italy

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AMC

Amsterdam, , Netherlands

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Jan van Goyen Medical Center

Amsterdam, , Netherlands

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Rijnstate Hospital

Arnhem, , Netherlands

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Hospital of Infectious Diseases of Warsaw

Warsaw, , Poland

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Hospital de Curry Cabral

Lisbon, , Portugal

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Hospital Santa Maria

Lisbon, , Portugal

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Hospital de Joaquim Urbano

Porto, , Portugal

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Hospital General Universitario de Alicante

Alicante, , Spain

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Hospital Clinic

Barcelona, , Spain

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Hospital de la Santa Creu I Sant Pau.

Barcelona, , Spain

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Hospital del Mar

Barcelona, , Spain

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Hospital Germans Trias i Pujol

Barcelona, , Spain

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Hospital Carlos III

Madrid, , Spain

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Hospital Clinico San Carlos

Madrid, , Spain

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Hospital Gregorio Marañon

Madrid, , Spain

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Hospital Universitario La Paz

Madrid, , Spain

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Hospital Universitario Virgen de la Victoria

Málaga, , Spain

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Hospital Universitario La Fe

Valencia, , Spain

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Sahlgrenska hospital

Gothenburg, , Sweden

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Karolinska hospital

Stockholm, , Sweden

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Venhälsan hospital

Stockholm, , Sweden

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Royal Bournemouth Hospital

Bournemouth, , United Kingdom

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Southmead Hospital

Bristol, , United Kingdom

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Western General Hospital

Edinburgh, , United Kingdom

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Mortimer market centre

London, , United Kingdom

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Royal Free Hospital

London, , United Kingdom

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Saint Mary's hospital

London, , United Kingdom

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Saint Stephen's Centre

London, , United Kingdom

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Saint Thomas hospital

London, , United Kingdom

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Countries

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Austria Belgium Denmark France Germany Greece Hungary Ireland Italy Netherlands Poland Portugal Spain Sweden United Kingdom

References

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Esteban-Cantos A, Rodriguez-Centeno J, Barruz P, Alejos B, Saiz-Medrano G, Nevado J, Martin A, Gaya F, De Miguel R, Bernardino JI, Montejano R, Mena-Garay B, Cadinanos J, Florence E, Mulcahy F, Banhegyi D, Antinori A, Pozniak A, Wallet C, Raffi F, Rodes B, Arribas JR; NEAT001/ANRS143 Study Group. Epigenetic age acceleration changes 2 years after antiretroviral therapy initiation in adults with HIV: a substudy of the NEAT001/ANRS143 randomised trial. Lancet HIV. 2021 Apr;8(4):e197-e205. doi: 10.1016/S2352-3018(21)00006-0.

Reference Type DERIVED
PMID: 33794182 (View on PubMed)

Ammassari A, Stohr W, Antinori A, Molina JM, Schwimmer C, Domingo P, Thalme A, Di Pietro M, Wallet C, Pozniak A, Richert L, Raffi F; NEAT001/ANRS143 Trial Study Group. Patient Self-Reported Adherence to Ritonavir-Boosted Darunavir Combined With Either Raltegravir or Tenofovir Disoproxil Fumarate/Emtricitabine in the NEAT001/ANRS143 Trial. J Acquir Immune Defic Syndr. 2018 Dec 1;79(4):481-490. doi: 10.1097/QAI.0000000000001834.

Reference Type DERIVED
PMID: 30365452 (View on PubMed)

Bernardino JI, Mocroft A, Mallon PW, Wallet C, Gerstoft J, Russell C, Reiss P, Katlama C, De Wit S, Richert L, Babiker A, Buno A, Castagna A, Girard PM, Chene G, Raffi F, Arribas JR; NEAT001/ANRS143 Study Group. Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial. Lancet HIV. 2015 Nov;2(11):e464-73. doi: 10.1016/S2352-3018(15)00181-2. Epub 2015 Sep 30.

Reference Type DERIVED
PMID: 26520926 (View on PubMed)

Raffi F, Babiker AG, Richert L, Molina JM, George EC, Antinori A, Arribas JR, Grarup J, Hudson F, Schwimmer C, Saillard J, Wallet C, Jansson PO, Allavena C, Van Leeuwen R, Delfraissy JF, Vella S, Chene G, Pozniak A; NEAT001/ANRS143 Study Group. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial. Lancet. 2014 Nov 29;384(9958):1942-51. doi: 10.1016/S0140-6736(14)61170-3. Epub 2014 Aug 4.

Reference Type DERIVED
PMID: 25103176 (View on PubMed)

Other Identifiers

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2009-015113-44

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2009-015113-44

Identifier Type: -

Identifier Source: org_study_id