ELDORADO

The challenge

An estimated 25 million people are living with HIV in sub-Saharan Africa and around 20 million are receiving antiretroviral therapy to control their infections. The most commonly used drug combination includes dolutegravir. Although very effective at suppressing viral replication, over the longer term, it has been found to lead to weight gain, metabolic conditions such as type 2 diabetes and hypertension, and an increased risk of cardiovascular disease and liver disease, particularly in women. Its use is also associated with sleep disturbance and mental health issues, leading to reduced quality of life. 

A new generation of antiretroviral drugs has been developed, including doravirine, which could be used instead of dolutegravir in combination therapies. Doravirine appears to be as effective as dolutegravir at suppressing viral replication but is associated with fewer metabolic complications.

Doravirine has been licensed and is in use in multiple high-income countries, but is not available in low- and middle-income countries, including sub-Saharan Africa. It has also not yet been directly compared with dolutegravir in a large-scale clinical trial.

The project

The ELDORADO project aims to generate the evidence that could underpin a switch from dolutegravir- to doravirine-containing antiretroviral therapy in sub-Saharan Africa (and in other countries in a related project).

The project is carrying out a trial comparing the use of dolutegravir- and doravirine-containing treatments in adults newly diagnosed with HIV infections. A total of 610 patients will be recruited at sites in Cameroon, Côte d’Ivoire, and Mozambique, as well as in other countries in a related project.

In addition to tracking the treatments’ effects on viral suppression, the trial incorporates a comprehensive assessment of their effects on key metabolic functions and weight gain, as well as cardiovascular and hepatic assessments, for around 22 months of treatment. Questionnaires will be used to collect data on the mental health and quality of life of participants. 

Data from this project and previous trials of doravirine will be collated to estimate the cost-effectiveness of the two options. 

Impact

The ELDORADO project will close an important gap relating to optimal HIV treatment in sub-Saharan Africa. It will: 

• Generate directly comparable data on doravirine- and dolutegravir-containing antiretroviral therapy.
• Provide data on the holistic impacts of treatments, including those relating to quality of life.
• Provide policymakers with a clear indication of the economic implications of the new treatment option.
• Train young researchers and health professionals in order to improve patients’ medical care.

WHO has indicated its support for the ELDORADO project, which will generate evidence that will feed directly into global and national policy on HIV treatment regimens.