How frequent is dolutegravir resistance?

Introduction: HIV remains a major global health concern. Unexpected disruptions in antiretroviral drug supply chains carry increased mortality and transmission risks. The integrase strand transfer inhibitor dolutegravir plays an increasingly critical role in the global fight against the epidemic. Its high barrier to resistance has been extensively documented in rich countries. Recent reports of resistance cases after dolutegravir failure in resource-limited cohorts raise concerns about whether its high barrier to resistance will hold in low-income countries.

Areas covered: For this review, we performed a search on the recent published literature and conference communications focused on acquired drug resistance against dolutegravir in low- and middle-income countries.

Expert opinion: Overall, the data unsurprisingly showed that resistance against dolutegravir emerged mainly from unsuppressed individuals with treatment adherence issues. This emergence happened at a population rate below 1% despite structural challenges. Almost half of the resistance cases involved the R263K substitution, which did not always preclude re-suppression with dolutegravir. Minor adjustments in the programmatic large-scale rollout of dolutegravir could further improve these outcomes. Continued treatment adherence support and the preservation of antiretroviral drug supply chains remain crucial for the success of HIV treatment.