Human Immunodeficiency Virus (HIV) integrase inhibitors (INI) are the most common drug class recommended by the different international guidelines as third agent of the combined antiretroviral therapy (cART). First licensed INI, raltegravir (RAL), is now available for 10 years and determinants of genotypic resistance are well-described for this drug, as well as for the second first-generation INI, elvitegravir (EVG). However, there is still data to provide regarding resistance mechanisms to the most recent, second-generation INI, dolutegravir (DTG).