DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection (ELDORADO)

Phase III, Open-label, Randomized, Multicenter Trial EvaLuating the Non-inferiority of DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

Phase III trial evaluating doravirine as an alternative to dolutegravir in treatment naïve people living with HIV-1 infection.

Study Overview

• Status: Recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Doravirine + tenofovir DF + lamivudine; Drug: Dolutegravir + tenofovir DF + lamivudine or emtricitabine

Detailed Description

Phase III, multicenter, open-label, randomized, non-inferiority clinical trial which aims to assess the non-inferiority of doravirine in association with tenofovir and lamivudine, as compared to dolutegravir in association with tenofovir and lamivudine or emtricitabine.

This trial will be implemented in Brazil, Cameroon, Côte d'Ivoire, France, Mozambique and Thailand.

Six hundred and ten patients will be enrolled and followed for 96 weeks after entry in the trial (=ART initiation).

Primary endpoint will assess virological efficacy at Week 48, measured by the proportion of subjects achieving HIV-1 RNA <50 copies/mL, in HIV-1 infected, treatment-naive subjects with pre-treatment viral load (HIV-1 RNA) ≥ 1,000 copies/mL.

Secondary endpoints are planned at W48 and W96.

• Study Type: Interventional
• Enrollment (Estimated): 610
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anthony L'HOSTELLIER; Phone Number: 33 (0)5 57 57 47 11; Email: anthony.lhostellier@u-bordeaux.fr
• Study Contact Backup: Name: Olivier MARCY, Dr; Phone Number: 33 (0)5 57 57 13 93; Email: olivier.marcy@u-bordeaux.fr

Study Locations

• Brazil
  • Rio de Janeiro
    • Nova Iguaçu, Rio de Janeiro, Brazil, 26030-380
      • Recruiting
      • Hospital Geral de Nova Iguaçu
      • Contact: Luis Eduardo FERNANDES, Dr; Phone Number: +55 21 997938393; Email: luisebcf@gmail.com
    • Rio de Janeiro, Rio de Janeiro, Brazil, 21040-900
      • Recruiting
      • Laboratory on Clinical research on AIDS-INI FIOCRUZ
      • Contact: Sandra WAGNER CARDOSO, Dr; Phone Number: +55 21 38 65 96 23; Email: sandra.wagner@ini.fiocruz.br
• Cameroon
  • Yaoundé, Cameroon
    • Recruiting
    • Hôpital Central de Yaoundé
    • Contact: Charles KOUANFACK, Pr; Phone Number: +237 699 95 07 43; Email: charleskouanfack@yahoo.fr
• Côte d’Ivoire
  • Abidjan, Côte d’Ivoire
    • Not yet recruiting
    • Centre de prise en charge de Recherche et de Formation (CEPREF)
    • Contact: Amani ANZIAN, Dr; Phone Number: +225 0140185774; Email: amani_anzian@yahoo.fr
  • Abidjan, Côte d’Ivoire
    • Not yet recruiting
    • Centre Médical de Suivi des Donneurs de Sang (CMSDS) - Centre National de Transfusion Sanguine (CNTS)
    • Contact: Albert KLA MINGA, Dr; Phone Number: +225 0140732382; Email: minga.kalbert@gmail.com
  • Abidjan, Côte d’Ivoire
    • Recruiting
    • CHU de Treichville, Service des Maladies Infectieuses et Tropicales (SMIT)
    • Contact: Serge EHOLIE, Pr; Phone Number: +2250708641080; Email: sergeholie@yahoo.fr
• France
  • Bordeaux, France, 33075
    • Recruiting
    • CHU Bordeaux Pellegrin - Service des Maladies Infectieuses et Tropicales
    • Contact: Charles CAZANAVE, Pr; Phone Number: +33 (0)5 56 79 55 36; Email: charles.cazanave@chu-bordeaux.fr
  • Bordeaux, France, 33075
    • Recruiting
    • CHU Bordeaux St André - Service de Médecine Interne
    • Contact: Fabrice BONNET, Pr; Phone Number: +33 (0)5 56 79 57 33; Email: fabrice.bonnet@chu-bordeaux.fr
  • Montpellier, France, 34295
    • Recruiting
    • CHU Montpellier - Hôpital La Colombière - Service des Maladies Infectieuses et Tropicales
    • Contact: Alain MAKINSON, Pr; Phone Number: +33 (0)4 67 33 95 10; Email: a-makinson@chu-montpellier.fr
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes Hôtel Dieu - Service des Maladies infectieuses et tropicales
    • Contact: Colin DESCHANVRES, Dr; Phone Number: +33 (0)2 40 08 31 10; Email: colin.deschanvres@chu-nantes.fr
  • Paris, France, 75010
    • Recruiting
    • AP-HP Hôpital Lariboisière - Service de Maladies Infectieuses et Tropicales
    • Contact: Pierre SELLIER, Dr; Phone Number: +33 (0)1 49 95 80 37; Email: pierre.sellier@aphp.fr
  • Paris, France, 75010
    • Recruiting
    • AP-HP Hôpital Saint Louis - Service des Maladies Infectieuses et Tropicales
    • Contact: Nathalie DE CASTRO, Dr; Phone Number: +33 (0)1 42 49 45 72; Email: nathalie.de-castro@aphp.fr
  • Paris, France, 75012
    • Recruiting
    • AP-HP Hôpital Saint Antoine - Service des Maladies Infectieuses et Tropicales
    • Contact: Karine LACOMBE, Pr; Phone Number: +33 (0)1 49 28 31 96; Email: karine.lacombe2@aphp.fr
  • Paris, France, 75013
    • Recruiting
    • AP-HP Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses et Tropicales
    • Contact: Valérie POURCHER, Pr; Phone Number: +33 (0)1 42 16 01 01; Email: valerie.martinez@aphp.fr
  • Paris, France, 75018
    • Recruiting
    • AP-HP Bichat Claude Bernard - Service des Maladies Infectieuses et Tropicales
    • Contact: Jade GHOSN, Pr; Phone Number: +33 (0)1 40 25 78 03; Email: jade.ghosn@aphp.fr
• Mozambique
  • Maputo, Mozambique
    • Recruiting
    • Centro de Saúde 1o de Maio
    • Contact: Neiva BANZE, Dr; Phone Number: + 258 84 053 3250; Email: neiva.banze@ins.gov.mz
• Thailand
  • Chiang Rai, Thailand, 57000
    • Not yet recruiting
    • Chiangrai Prachanukroh
    • Contact: Suwimon KHUSUWAN, Dr; Phone Number: +66 814865047; Email: ngornaja@yahoo.com
  • Lampang, Thailand, 52000
    • Not yet recruiting
    • Lampang Hospital Internal Medicine department
    • Contact: Parichart SAKULKONKIJ, Dr; Phone Number: +66815958662; Email: parichart1507@gmail.com
  • Phayao, Thailand, 56000
    • Not yet recruiting
    • Phayao Hospital Internal Medicine department
    • Contact: Guttiga HALUE, Dr; Phone Number: +6689933568; Email: drgutti@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be at least 18 years of age on the day of signing the informed consent.
• Be HIV-1 positive as determined according to national testing strategies
• Have a plasma HIV-1 RNA ≥1000 copies/mL within 30 days prior to the randomization,
• Have HIV treatment indication based on physician assessment according to local treatment guidelines
• Be naïve to antiretroviral therapy (ART) including investigational antiretroviral agents
• For women or transgender men of childbearing potential i.e. of childbearing age who are not menopausal, or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or not refraining from sexual activity: negative urinary test for pregnancy and acceptance to use contraceptive methods
• Understand the study procedures and voluntarily agree to participate by giving written informed consent for the trial.

Non-inclusion Criteria:

• Has ongoing (pulmonary or extra-pulmonary) tuberculosis
• Has any other history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
• Is infected with HIV-2 or co-infected with HIV-1 and HIV-2
• Has received cabotegravir long acting or dapivirine pre-exposure prophylaxis (PrEP).
• Has received oral pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) in the past three months or has had no negative HIV-1 serology performed
• Has documented or known resistance or possible resistance to study drugs (in France and where national guidelines recommend screening for primary resistance before starting first-line ART) as defined by the ANRS MIE AC43 Resistance group

• Has the following laboratory values at screening visit, within 30 days prior to the randomization:

  • AST (SGOT) and ALT (SGPT) >4.0 x upper limit of normal
  • Estimated glomerular filtration rate at time of screening <60 mL/min/1.73m², based on the CKD-EPI equation
• Has participated in a study with an investigational compound/device within 30 days prior to signing informed consent or anticipates participating in such a study involving an investigational compound/device during the course of this study.
• Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
• Requires or is anticipated to require any of the prohibited or contraindicated medications noted in the trial protocol.
• Has significant hypersensitivity or other contraindication to any of the components of the study drugs.
• Is pregnant, breastfeeding, or expecting to conceive at any time during the study.
• Has any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to study procedure.
• Is a person under guardianship or deprived of freedom by a judicial or administrative decision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doravirine arm; Doravirine (100 mg) + tenofovir DF (300 mg) + lamivudine (300mg) administered daily	Drug: Doravirine + tenofovir DF + lamivudine; Oral administration; Other Names: Delstrigo
Active Comparator: Dolutegravir arm; Dolutegravir (50 mg) + tenofovir DF 300 mg + XTC (300 mg if lamivudine or 200 mg if emtricitabine) administered daily	Drug: Dolutegravir + tenofovir DF + lamivudine or emtricitabine; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of doravirine in combination with tenofovir and lamivudine as compared to dolutegravir in combination with tenofovir and lamivudine or emtricitabine in terms of virological efficacy at week 48	The non-inferiority will be assessed in terms of virologic efficacy at week 48 under allocated treatment using the FDA snapshot algorithm (window period of 42-54 weeks), and measured by the proportion of subjects achieving a rate of HIV 1 RNA <50 copies/mL, in HIV-1 infected, treatment-naive subjects with pre-treatment viral load (HIV-1 RNA) ≥ 1,000 copies/mL. The rate of HIV 1 RNA will be measured by RT-PCR.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of obesity	Obesity will be defined as having BMI≥30 kg/m² for Caucasian and African population and BMI≥27.5 kg/m² for Asian populations.	Week 48; Week 96
Occurrence of insulin resistance	Proportion of subjects with newly measured HOMA≥2 as compared to baseline HOMA will be calculated with the following formula (glucose levels in mmol/L, insulin levels in mIU/L): HOMA =(glucose ×insulin)÷22.5	Week 48; Week 96
Occurrence of hypertension	Proportion of subjects with hypertension newly detected compared to baseline. Hypertension will be defined as either being prescribed new anti-hypertension medication and/or by having diastolic blood pressure >90 mmHg AND/OR systolic blood pressure >140 mmHg during visit and confirmed during subsequent visit > 15 days after.	Week 48; Week 96
Non-inferiority of DOR in association with TDF and 3TC, compared to DTG in association with TDF and 3TC or FTC, in terms of virologic efficacy	Proportion of subjects in virologic success defined as achieving HIV-1 RNA <50 copies/mL at week 96 under allocated treatment using the FDA snapshot algorithm with a window period of 90 to 102 weeks; subjects not achieving viral success will be described according to the FDA snapshot recommendation	Week 96
Occurrence of virological failures	Proportion of confirmed virological failures. Virological failure will be defined as 1) confirmed HIV-1 RNA ≥ 200 copies/mL after initial response with HIV-1 RNA < 50 copies/mL at any time during the study or 2) non-response defined as either confirmed HIV-1 RNA ≥ 200 copies/mL at Week 24 or Week 36 (or any other unscheduled visit in-between) or confirmed HIV-1 RNA ≥ 50 copies/mL at Week 48, Week 72 and Week 96 (or any other unscheduled visit in-between).	Virological failure
Occurrence of HIV-1 drug resistances in patients with confirmed virological failure	Frequency of HIV-1 drug resistances in participants with a confirmed virological failure. Drug resistances will be defined according to the last version of the ANRS algorithm and to the last version of the Stanford algorithm.	Virological Failure
Virological efficacy at a threshold of HIV 1 RNA<200 copies/mL	Proportion of subjects achieving HIV 1 RNA<200 copies/mL under allocated treatment	Week 48; Week 96
Virological efficacy at a threshold of HIV 1 RNA<1000 copies/mL	Proportion of subjects achieving HIV 1 RNA<1000 copies/mL under allocated treatment	Week 48; Week 96
Effect of baseline RT and integrase mutations on virological response	Frequency of RT and integrase mutations at baseline and impact on the virological response	Week 48; Week 96
Occurrence of combined overweight and obesity	Combined overweight and obesity will be defined as having BMI≥25 kg/m² for Caucasian and African populations and BMI≥23 kg/m² for Asian populations	Week 48; Week 96
Occurrence of weight gain ≥10% absolute body weight	Proportion of subjects with ≥10% absolute weight gain from baseline	Week 48; Week 96
Changes in absolute weight gain	Absolute weight gain will be calculated by simply subtracting the follow-up weight from baseline weight measured according to protocol procedures	Week 48; Week 96
Occurrence of diabetes	Proportion of subjects with diabetes newly detected compared to baseline. Diabetes will be defined as either being prescribed new medication for diabetes mellitus and/or having a fasting glycemia ≥1.26 g/L during visit and confirmed during subsequent visit > 15 days after and/or in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L).	Week 48; Week 96
Safety and tolerability	Any adverse event of any grade and those graded 3-4	Week 48; Week 96
Changes in waist circumference, hip circumference and waist-to-hip ratio	Change from baseline in waist and hip circumferences and waist-to-hip ratio	Week 48; Week 96
Changes in fasting glycemia and insulin	Change from baseline in fasting glycemia and insulin	Week 48; Week 96
Changes in fasting serum lipids	Change from baseline in fasting serum lipids. The fasting serum lipids analyzed will be total cholesterol, HDL, LDL and triglycerides.	Week 48; Week 96
Changes in estimated glomerular filtration rate	Change from baseline in estimated glomerular filtration rate. Estimated glomerular filtration rate (eGFR) will be calculated using the CKD-EPI equation	Week 48; Week 96
Occurrence of cardiovascular abnormalities	Change from baseline in cardiovascular parameters (blood pressure profile, electrocardiographic and echocardiographic damages). These cardiovascular parameters assessments will be measured through an electrocardiogram, a transthoracic echocardiography and an ABPM, a 24-hour blood pressure Holter.	Week 48; Week 96
Changes in liver steatosis and clinically significant fibrosis	Change from baseline in mean patient CAP and LSM measurements and occurrence of: Liver steatosis defined by CAP ≥ 263 dB/m2, and clinically significant liver fibrosis and cirrhosis defined by LSM ≥ 8.0 kPa and LSM ≥ 12.5 kPa, respectively	Week 48; Week 96
Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic-associated steatohepatitis (MASH)	Change from baseline in mean patient CAP and LSM measurements and occurrence of: MASLD defined by the presence of liver steatosis with at least one cardiometabolic risk-factor (overweight/obesity; pre-or diabetes; hypertension; hypertriglyceridemia or low-HDL; and MASH defined by the presence of at least CSF in people with MASLD.	Week 48; Week 96
Changes in liver diseases biomarkers	Changes from baseline in Fib-4, VCTE and FAST scores and presence at baseline or occurrence of: CSF defined as Fib-4 ≥ 2.67 and FAST score > 0.67 (high probability of MASH)	Week 48; Week 96
Changes in mental health and quality of life outcomes	Change from baseline in EQ-5D-3L, HIVTSQ, DASS-21, PSQI, WHOQOL HIV-BREF scores	Week 24; Week 48; Week 96
Occurrence of Acquired Immune Deficiency Syndrome (AIDS), tuberculosis, Immune Reconstitution Inflammatory Syndrome (IRIS) or death	Proportion of subjects with AIDS (defined as having CDC stage 3/C or WHO stage 4), tuberculosis, IRIS or death	Week 48; Week 96
Description of antiretroviral drugs trough plasma concentration in each arm	DOR, DTG and M9 trough plasma concentration in samples taken pre-dose	Week 4; Week 24; Week 48; Week 96
Assessment of the effect of antiretroviral drugs trough plasma concentration on virological response	DOR, DTG and M9 trough plasma concentration in samples taken pre-dose	Week 4; Week 24; Week 48; Week 96
Determining DOR, DTG and M9 trough plasma concentration thresholds predictive of virological response	DOR, DTG and M9 trough plasma concentration in samples taken pre-dose	Week 4; Week 24; Week 48; Week 96
Assessment of the effect of antiretroviral drugs trough plasma concentration on safety endpoints	DOR, DTG and M9 trough plasma concentration in samples taken pre-dose	Week 4; Week 24; Week 48; Week 96
Changes in CD4 cell count, CD4 percentage, CD8 cell count, CD8 percentage, CD4/CD8 ratio	Change from baseline in CD4 cell count, CD4 percentage, CD8 cell count, CD8 percentage, CD4/CD8 ratio	Week 48; Week 96
Adherence to ART	Adherence to ART by (1) pill count (considering a pill count adherence ratio <95% as sub-optimal adherence), (2) 4-days and 1-month recall questions at every trial visit, (3) by TFV-DP quantification in dried blood spots (LC/MS). ARV pill burden will also be an endpoint in order to study the relation between adherence and ARV pill burden.	Week 48; Week 96
Description of the distribution of CYP3A5/4 mutations according to ARV regimen	Type and frequency of alleles variants in the gene coding for CYP3A5/4	Study long
Assessment of the impact of CYP3A5/4 mutations on PK	Impact of CYP3A5/4 mutations on pharmacokinetics of DOR, DTG and M9	Study long
Assessment of the impact of CYP3A5/4 mutations on virological response and side effects	Virological response and side-effects depending on CYP3A5/4 mutations	Study long
Explore additional polymorphism (i.e. UGT1A1) according to literature update	Assess additional polymorphism of UGT1A1	Baseline
Cost-effectiveness and budget impact of using DOR-based versus DTG-based antiretroviral regimens	Cost-effectiveness measured by (1) Incremental health benefits of using one regimen compared to the other (in DALYs and QALYs), (2) Incremental economic costs of using one regimen compared to the other (USD), (3) Budget impact of changing from one regimen to the other (USD)	Study long
Changes in truncal fat distribution in a sub-group of cisgender women enrolled in the trial	Change from baseline in truncal fat distribution. Truncal fat repartition will be measured by the proportion of fat tissue using DEXA-scanner assessment	Week 48; Week 96
Changes in adipose tissue markers and immune activation markers in a sub-group of cisgender women enrolled in the trial	Change from baseline in adipose tissue markers (adiponectin, leptin) and immune activation markers (sCD14, sCD163). Measurement will be made on stored serum samples by immunonephelometry or ELISA.	Week 48; Week 96
Changes in fat quality in a sub-group of cisgender women enrolled in the trial	Change from baseline (by abdominal subcutaneous surgical biopsy) in fat pathology, gene expression and global transcriptome analysis (RT-PCR and RNAseq). Measurement will be made on an abdominal fat tissue biopsy sample fixed for immunohistochemistry (Red Sirius, collagen 6, fibronectine, TFG-beta, alpha-SMA) and frozen for gene expression analysis by RT-PCR of markers of adipogenesis (PPARG, CEPBA), beiging (PRDM16, PGC1A), lipogenesis (FAS), adipocyte function (GLUT4), fibrosis (COL4, COL6, FN, TGFB, LOX, ASMA) and mDNA level (mDNA gene and nDNA).	Week 48

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: European and Developing Countries Clinical Trials Partnership (EDCTP); MSD France
• Investigators: Principal Investigator: Pierre SELLIER, Dr, Assistance Publique - Hôpitaux de Paris; Principal Investigator: Beatriz GRINSZTEJN, Pr, Ini-Fiocruz

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: HIV-1; dolutegravir; non-inferiority; doravirine; ART-naïve
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Immune System Diseases; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Infections; Communicable Diseases; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Organophosphorus Compounds; Nucleosides; Deoxyribonucleosides; Organophosphonates; Adenine; Dideoxynucleosides; Zalcitabine; Tenofovir; Emtricitabine; Lamivudine; dolutegravir; doravirine
• Other Study ID Numbers: ANRS 0392s ELDORADO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No