HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre longitudinal study (DTG RESIST).

- DTG RESIST is a large international study to prospectively examine emergent dolutegravir resistance in diverse settings characterised by different HIV-1 subtypes, provision of ART, and guidelines on resistance testing. - Embedded within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST will benefit from harmonized clinical data across participating sites and expertise in clinical, epidemiological, biological, and computational fields. - Procedures for sequencing and assembling genomes from different HIV-1 strains will be developed at the heart of the HIV epidemic, by the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), in Durban, South Africa. Phenotypic testing, Genome Wide Association Study (GWAS) methods and Bayesian evolutionary models will explore and predict treatment failure genotypes. - A significant limitation is the absence of genotypic resistance data from participants before they started dolutegravir treatment, as collecting and bio-banking pre-treatment samples was not feasible at most IeDEA sites. Consistent and harmonized data on adherence to treatment are also lacking. - The distribution of HIV-1 subtypes across different sites is uncertain, which may limit the statistical power of the study in analysing patterns and risk factors for dolutegravir resistance. The results from GWAS and Bayesian modelling analyses will be preliminary and hypothesis-generating.