The emergence and spread of drug resistance, particularly Dolutegravir-resistant HIV, is a major threat to ending the global HIV epidemic. Dolutegravir (DTG) is an antiretroviral medicine used in combination with other drugs for the treatment of HIV infections. Since DTG offers a high barrier to the development of drug resistance, the global HIV response relies heavily on this treatment. For this reason, it is vital to understand how DTG-resistance emerges among people with different HIV subtypes and within different clinical contexts.
The project’s interrelated goals include determining contexts where DTG-resistance emerges, establishing IeDEA as an early detection and warning system for drug resistance, and safeguarding the long-term sustainability of the global HIV response.
To achieve these goals, the highly complex study will compare data from nine established HIV cohorts with samples from nearly 4,600 participants from 32 countries. Adults and adolescents under DTG-based antiretroviral treatment who experience virologic failure will be enrolled in IeDEA region studies. Then, small blood samples will be sent for drug-resistance testing at the Kwazulu-Natal Research Innovation and Sequencing Platform in South Africa. The complex mutational patterns will be analysed later in Switzerland using Conjunctive Bayesian Networks methodology.
Egger will lead ISPM’s work along with experts from University of Kwa Zulu Natal (South Africa), University of Zurich and ETH Zurich (Switzerland), and University of Bristol (UK). With these partners, the project will combine the latest advancements in whole genome sequencing with expertise from clinical, epidemiological, biological, and computational science.