Clinical trial NCT01066962: Study of Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir in HIV-infected Antiretroviral naïve Subjects
Official title: An Open-label Randomised Two-year Trial Comparing Two First-line Regimens in HIV-infected Antiretroviral naïve Subjects: Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir (ANRS 143/NEAT 001)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV-infected antiretroviral naïve subjects
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: NEAT - European AIDS Treatment Network
First posted: 2010-02-10
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Non-inclusion Criteria:

* 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

Primary outcomes:
measure: Time to virologic or clinical failure, as the first occurrence of one of six protocol-defined components
timeFrame: minimum 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Wien
country: Austria
facility: Otto Wagner Spital mit Pflegezentrum
city: Antwerpen
country: Belgium
facility: ITZ Antwerpen
city: Brussels
country: Belgium
facility: CHU Saint Pierre
city: Gent
country: Belgium
facility: UZ Gent
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Bordeaux
country: France
facility: Hôpital Saint André
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: Hôpital du Bocage
city: Fort de France
country: France
facility: Hôpital Pierre Zobda-Quitman
city: La Roche sur Yon
country: France
facility: CHD de la Roche sur Yon
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
city: Nantes
country: France
facility: Hôpital de l'Hôtel Dieu
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou (HEGP)
city: Paris
country: France
facility: Hôpital La Pitié Salpétrière
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Saint Louis
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Suresnes
country: France
facility: Hôpital Foch
city: Toulouse
country: France
facility: Hôpital Purpan
city: Tourcoing
country: France
facility: Hôpital Gustave Dron
city: Berlin
country: Germany
facility: Gemeinschaftspraxis Jessen-Jessen-Stein
city: Bonn
country: Germany
facility: Med. Universitätsklinik I
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe Universität
city: Hamburg
country: Germany
facility: Asklepios-Klinik St. Georg
city: Hamburg
country: Germany
facility: ICH study centre
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Köln
country: Germany
facility: Universitätsklinik Köln
city: Athens
country: Greece
facility: Attikon University Hospital
city: Athens
country: Greece
facility: Evaggelismos General Hospital
city: Athens
country: Greece
facility: Laikon General Hospital
city: Budapest
country: Hungary
facility: Saint Laszlo Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae
city: Dublin
country: Ireland
facility: St James's Hospital
city: Brescia
country: Italy
facility: University of Brescia
city: Florence
country: Italy
facility: Ospedale Santa Maria Annunziata
city: Milano
country: Italy
facility: Luigi Sacco Hospital
city: Milan
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Milan
country: Italy
facility: San Paolo Hospital
city: Rome
country: Italy
facility: Istituto Naziona e per le Malattie "Lazzaro Spallanzani"
city: Rome
country: Italy
facility: Sapienza Universita di Roma
city: Rome
country: Italy
facility: Torvergata University
city: Turin
country: Italy
facility: Ospedale "Amedeo di Savoia"
city: Amsterdam
country: Netherlands
facility: AMC
city: Amsterdam
country: Netherlands
facility: Jan van Goyen Medical Center
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Warsaw
country: Poland
facility: Hospital of Infectious Diseases of Warsaw
city: Lisbon
country: Portugal
facility: Hospital de Curry Cabral
city: Lisbon
country: Portugal
facility: Hospital Santa Maria
city: Porto
country: Portugal
facility: Hospital de Joaquim Urbano
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau.
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital Carlos III
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Gothenburg
country: Sweden
facility: Sahlgrenska hospital
city: Stockholm
country: Sweden
facility: Karolinska hospital
city: Stockholm
country: Sweden
facility: Venhälsan hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: Mortimer market centre
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Saint Mary's hospital
city: London
country: United Kingdom
facility: Saint Stephen's Centre
city: London
country: United Kingdom
facility: Saint Thomas hospital
Study officials:
affiliation: Nantes University Hospital
name: François Raffi, Professor
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.