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. 2018 Oct 25;8:15751. doi: 10.1038/s41598-018-33538-0

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Direct acyclic graph (DAG) showing the relationship between prior ARV use, pre-treatment drug resistance and virological failure. P represents direct effects of prior ARV use on virological failure. Q represents indirect effects of prior ARV use on virological failure mediated through pre-treatment drug resistance. R represents confounders of the association between prior ARV use and virological failure: age and sex. S represents confounders of the association between pre-treatment drug resistance and virological failure that are affected by prior ARV use: pre-treatment viral load, CD4 cell counts and adherence. T represents confounders of the association between pre-treatment drug resistance and virological failure not included in S: type of initial antiretroviral treatment (NNRTI and NRTI) initiated and calendar year of treatment initiation. U represents unmeasured confounders. We note that the DAG is only a simple illustration and this may exclude complex relationships interacting between prior ARV use/pre-treatment drug resistance/virological failure and their confounders.