{
  "abstract": "Introduction Increasing evidence suggests that dolutegravir (DTG), endorsed by the WHO since 2018 for first-line antiretroviral therapy (ART), is associated with significant weight gain and potentially also with cardiometabolic disorders. In an effort to expand therapeutic options for people living with HIV (PLHIV), the EvaLuating the non-inferiority of DORAvirine vs DOlutegravir trial aims to compare the virologic efficacy of doravirine (DOR) and DTG-based regimens and to assess their safety, including a focus on cardiometabolic effects.Methods and analysis This is an international, phase III, multicentre, open-label, non-inferiority, randomised trial that will enrol 610 ART-naïve PLHIV (HIV RNA≥1000 copies/mL at screening) across six countries (Brazil, Cameroon, France, Côte d’Ivoire, Mozambique and Thailand) spanning four continents. Key inclusion criteria include age ≥18 years, confirmed HIV-1 infection with plasma RNA levels ≥1000 copies/mL, indication for ART initiation and no prior ART exposure. Participants will be randomised in a 1:1 ratio to receive either DOR 100 mg once daily in combination with tenofovir disoproxil fumarate (TDF) (300 mg daily) plus lamivudine (3TC) (300 mg daily) or DTG (50 mg daily) in combination with TDF (300 mg once daily) plus either emtricitabine (FTC) (200 mg daily) or 3TC (300 mg daily). Randomisation will be stratified by screening HIV-1 RNA load (≤100 000 or >100 000 copies/mL) and by country. The primary outcome is virological efficacy, defined as the proportion of participants achieving HIV-1 RNA <50 copies/mL at week 48 on the assigned treatment (FDA Snapshot algorithm). Secondary outcomes include cardiometabolic safety endpoints (ie, weight gain, insulin resistance, hypertension, diabetes, waist and hip circumferences, waist-to-hip ratio, fasting glycaemia, insulin and fasting serum lipids), along with mental health, quality of life, virological and immunological parameters. Final data collection is expected by July 2028.Ethics and dissemination Primary outcome results (week 48) are expected in early 2028. The project was submitted to and approved by national ethics committees and pharmaceutical regulatory authorities in all participating countries: Brazil (CEP INI FIOCRUZ (21.040-900)/CEP HGNI (26.030-380)); Cameroon (CNERSH (2024/09/1717/CE/CNERSH/SP)/Ministry of Public Health (D30-1464/AAR/MINSANTE/SG/DROS/CRC); Côte d'Ivoire: (CNESVS (0018224/MSHPCMU/CNESVS-km)/AIRP (1329/AIRP/DISMP/Om/kbaag); France (CTIS CPP/ANSM (2023-508626-10-00)); Mozambique (CNBS (20/CNBS/25)/ANARME (4635/380/ANARME)); Thailand: (IHRP (08/1944)/Thai FDA: ongoing on 19 January 2026). The trial received authorisation from the French National Commission for Data Protection and Liberties (CNIL) under approval number 924 302. Written informed consent is obtained from all participants prior to any study-specific procedures and trial enrolment, in accordance with the Declaration of Helsinki and applicable national regulations. Study findings will be disseminated through publication in peer-reviewed journals and presentations at national and international scientific conferences. Results will also be communicated to policymakers, healthcare professionals, community stakeholders and study participants through appropriate dissemination activities, including policy briefs, stakeholder meetings and lay summaries on dedicated and easily accessible platforms.Trial registration numbers NCT06203132; EU-CT, 2023-508626-10-00.",
  "authors": [
    {
      "affiliations": [
        "National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France"
      ],
      "name": "Anthony L’hostellier"
    },
    {
      "affiliations": [
        "Faculty of Medicine and Pharmaceutical Sciences, Université de Dschang, Yaounde, Cameroon"
      ],
      "name": "Charles Kouanfack"
    },
    {
      "affiliations": [
        "National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France"
      ],
      "name": "Corine Chazallon"
    },
    {
      "affiliations": [
        "STDs/AIDS Clinical Research Laboratory, Oswaldo Cruz Foundation, National Institute of Infectology (INI), Rio de Janeiro, Brazil"
      ],
      "name": "Sandra Wagner-Cardoso"
    },
    {
      "affiliations": [
        "Department of Infectious and Tropical Diseases, CHU de Treichville, Abidjan, Côte d’Ivoire"
      ],
      "name": "Serge Paul Eholie"
    },
    {
      "affiliations": [
        "Instituto Nacional de Saúde, Maputo, Mozambique"
      ],
      "name": "Neiva Banze"
    },
    {
      "affiliations": [
        "Internal Medicine Department, Department of Medical, Phayao Hospital, Mueang Phayao District, Thailand"
      ],
      "name": "Guttiga Halue"
    },
    {
      "affiliations": [
        "Inserm UMR_S938, CRSA, ICAN, Sorbonne Universite, Paris, France"
      ],
      "name": "Jacqueline Capeau"
    },
    {
      "affiliations": [
        "Virology Department, Assistance Publique - Hopitaux de Paris, Paris, France"
      ],
      "name": "Constance Delaugerre"
    },
    {
      "affiliations": [
        "Programme PAC-CI, Abidjan, Côte d’Ivoire"
      ],
      "name": "Raoul Moh"
    },
    {
      "affiliations": [
        "National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France",
        "Hôpital St-André, Internal Medicine and Infectious Diseases Department, CHU de Bordeaux, Bordeaux, France"
      ],
      "name": "Fabrice Bonnet"
    },
    {
      "affiliations": [
        "Universite de Yaounde I Faculte de Medecine et des Sciences Biomedicales, Yaounde, Cameroon"
      ],
      "name": "Liliane Mfeukeu Kuate"
    },
    {
      "affiliations": [
        "National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France"
      ],
      "name": "Antoine Jaquet"
    },
    {
      "affiliations": [
        "STDs/AIDS Clinical Research Laboratory, Oswaldo Cruz Foundation, National Institute of Infectology (INI), Rio de Janeiro, Brazil"
      ],
      "name": "Hugo Perazzo"
    },
    {
      "affiliations": [
        "National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France"
      ],
      "name": "Charlotte Bernard"
    },
    {
      "affiliations": [
        "Department of Biochemistry - Pharmacology, Assistance Publique - Hopitaux de Paris, Paris, France",
        "INSERM UMR 955 and UPEC, Faculty of Health, Créteil, France"
      ],
      "name": "Jean-Philippe Bastard"
    },
    {
      "affiliations": [
        "Pharmacology Department, Saint-Louis Hospital, GHU AP-HP Nord Université Paris Cité, Paris, France"
      ],
      "name": "Lauriane Goldwirt"
    },
    {
      "affiliations": [
        "Pharmacology Department, Saint-Louis Hospital, GHU AP-HP Nord Université Paris Cité, Paris, France"
      ],
      "name": "Paul Vilquin"
    },
    {
      "affiliations": [
        "Delegação Provincial da Cidade de Maputo, Instituto Nacional de Saúde, Maputo, Mozambique"
      ],
      "name": "Pedroso Pedro Nhassengo"
    },
    {
      "affiliations": [
        "Agence Nationale de Recherches sur le sida et les hépatites virales ANRS|Maladies infectieuses émergentes, Paris, France"
      ],
      "name": "Margot Lavalée"
    },
    {
      "affiliations": [
        "Agence Nationale de Recherches sur le sida et les hépatites virales ANRS|Maladies infectieuses émergentes, Paris, France"
      ],
      "name": "Nicolas Minvielle"
    },
    {
      "affiliations": [
        "School of Health and Related Research, University of Sheffield, Sheffield, UK"
      ],
      "name": "P J Dodd"
    },
    {
      "affiliations": [
        "National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France"
      ],
      "name": "Olivier Marcy"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, AP-HP Saint-Louis and Lariboisière Hospitals, Paris, France",
        "Paris Cité University, Paris, France"
      ],
      "name": "Jean-Michel Molina"
    },
    {
      "affiliations": [
        "STDs/AIDS Clinical Research Laboratory, Oswaldo Cruz Foundation, National Institute of Infectology (INI), Rio de Janeiro, Brazil"
      ],
      "name": "Beatriz Grinsztejn"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, AP-HP Saint-Louis and Lariboisière Hospitals, Paris, France",
        "Paris Cité University, Paris, France"
      ],
      "name": "Pierre O Sellier"
    }
  ],
  "title": "Doravirine versus dolutegravir-based regimen in antiretroviral treatment-naive people living with HIV-1 (ANRS0392s ELDORADO): protocol for an international, open-label, randomised, non-inferiority, phase III trial",
  "uid": "4515710f-0b26-5868-bdf0-e95f0b55eaf7"
}