Pham HT, et al. - Dolutegravir (DTG) demonstrates high genetic barrier to resistance, hence it has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. In patients who experienced virological failure while using DTG monotherapy, researchers determined the underlying mechanism related to the emergence of a S230R substitution. The S230R substitution was comparable to the previously reported R263K in some respects. The occurrence of virological failure under DTG monotherapy via the development of such S230R or R263K mutations was observed without the need for high levels DTG resistance.