Will drug resistance against dolutegravir in initial therapy ever occur?

Dolutegravir (DIG) is a second-generation integrase strand transfer inhibitor (INSTI) and INSTIs are the latest class of potent anti-HIV drugs. Compared to the first generation INSTIs, raltegravir, and elvitegravir, DIG shows a limited cross-resistance profile. More interestingly, clinical resistance mutations to DIG in treatment-naive patents have not been observed to this date. This review summarizes recent studies on resistance mutations to DIG and on our understanding of the mechanisms of resistance to DIG as well as future directions for research.