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Toxicity of dolutegravir and evaluation of doravirine for alternative 1st line antiretroviral treatment in people living with HIV

Project description

Rethinking HIV treatment to safeguard health

Dolutegravir (DTG) is widely used as a first-line HIV treatment, but growing evidence links it to serious side effects, including obesity, diabetes, and hypertension, particularly among women in sub-Saharan Africa. These health risks, alongside mental health and quality-of-life concerns, demand urgent attention. With this in mind, the EU-funded ELDORADO project is investigating doravirine (DOR), a promising but underused alternative. Through a major clinical trial spanning Africa, Asia, Europe, and South America, the project will compare the safety and effectiveness of DOR-based therapies against DTG. It also explores long-term organ effects, mental health, and economic impact, aiming to inform global HIV treatment guidelines and improve outcomes for millions of people living with HIV worldwide.

Objective

The integrase inhibitors dolutegravir (DTG) is recommended by the World Health Organization (WHO) for 1st line antiretroviral therapy (ART) in people living with HIV (PLHIV) since 2018. Despite its high virologic efficacy, there is growing evidence showing massive weight gain and high incidence of metabolic disorders (obesity, type 2 diabetes) and hypertension under DTG, notably among women from sub-Saharan Africa (SSA) women, along with mental health and quality of life issues. The non-nucleoside reverse transcriptase inhibitor doravirine (DOR) is a potent novel ART, recommended in European and North-American guidelines, but not used so far in Southern countries despite interesting virological, safety and resistance profiles. In this context, the ELDORADO project will generate high-quality data on DTG-based ART toxicity and evaluate DOR as an alternative for 1st-line HIV-1 treatment in order to support national and international policymakers in updating national and international guidelines and practices aimed to improve patient outcomes and reduce disease burden of HIV in sub-Saharan Africa and worldwide. The project includes i) a randomized clinical trial assessing the non-inferiority of DOR-based ART as compared to DTG-based ART in terms of virologic efficacy, and its superiority in terms of key safety endpoints (obesity, diabetes, hypertension) in 610 PLHIV from diverse ethnic backgrounds across in SSA (Cameroon, Côte d’Ivoire, Mozambique), Brazil, Thailand, and France, ii) innovative assessments of organ lesions, iii) assessments of mental health and quality of life, iv) health impact and economics modelling based on the trial results as well as that of other trials (NAMSAL) and cohorts (IeDEA West Africa and Brazil). The project will also prioritize capacity building for junior investigators and community advisory board. The ELDORADO trial will be confounded in non-SSA countries by the ANRS|MIE (trial sponsor) and MSD, and benefits from support from the WHO.

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Programme(s)

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Topic(s)

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HORIZON-JU-RIA - HORIZON JU Research and Innovation Actions

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Call for proposal

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(opens in new window) HORIZON-JU-GH-EDCTP3-2024-01-two-stage

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Coordinator

UNIVERSITE DE BORDEAUX
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 132 755,00
Address
PLACE PEY BERLAND 35
33000 BORDEAUX
France

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Region
Nouvelle-Aquitaine Aquitaine Gironde
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 538 255,00

Participants (6)

Partners (4)

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