Toxicité du dolutégravir et évaluation de la doravirine comme alternative au traitement antirétroviral de première ligne chez les personnes vivant avec le VIH – ELDORADO

The integrase inhibitor (INSTI) dolutegravir (DTG) is recommended by the World Health Organization since 2018 as first-line antiretroviral therapy (ART) in adults living with HIV-1. Growing evidences show that DTG-based ART is associated with massive
weight gain, hypertension and diabetes, notably among women from Sub-Saharan Africa. There is an urgent need for an alternative first line ART for people living with HIV.
The non-nucleoside reverse transcriptase inhibitor (NNRTI) doravirine (DOR) is a potent novel ART, part of European and American guidelines but is not used in South countries despite interesting virological, safety and resistance profile.
The ELDORADO project aims to implement a randomized clinical trial to compare DOR with DTG in ART-naïve, HIV-1 infected subjects and enroll 610 ethnically diverse participants over 6 countries (Brazil, Cambodia, Cameroon, Côte d’Ivoire, France and Mozambique). This trial will be sponsored and co-funded by the ANRS MIE. Co-funding through EDCTP3 will enable the trial to be implemented in Sub-Saharan Africa and fund key assessments in order to provide high quality data to national and international policies.
To address this main objective, the ELDORADO project will assess: i) non-inferiority of DOR as compared to DTG ii) occurrence of cardiometabolic and hepatic disorders; iii) metabolic changes in adipose tissue and immune activation markers in a sub-group of women; iv) pharmacokinetics and pharmacodynamics on virological and safety endpoints, and pharmacogenetics of DOR and DTG; v) long term health impact of DTG, cost-effectiveness and market access to DOR; vi) capacity building for junior investigators and community advisory boards.
If virological non-inferiority is confirmed with superiority in terms of safety, DOR might be a preferred choice in some populations to avoid adverse events related to metabolic changes due to INSTI-based regimen. This will provide data to update national and
international guidelines.