Curbing the Rise of HIV Drug Resistance in Low-income and Middle-income Countries: the Role of Dolutegravir-containing Regimens

To improve virological suppression and address the emerging threat of HIV drug resistance, many low-income and middle-income countries are moving away from non-nucleoside reverse transcriptase inhibitors (NNRTI) and transitioning to dolutegravir as part of a more affordable and standardised antiretroviral therapy (ART). Although this transition could decrease the effect of rising NNRTI resistance and yield improved ART outcomes, it also presents new challenges. First, current safety concerns for dolutegravir use in women of childbearing potential require alternative solutions. Second, pre-existing resistance to the co-administered nucleoside reverse transcriptase inhibitors might reduce effectiveness and durability of dolutegravir, particularly if there is scarce access to viral load tests to monitor treatment outcomes. Third, there is inadequate information on the genetic correlates of resistance to dolutegravir, particularly in patients infected with HIV-1 non-B subtypes. Finally, clinical management of patients with confirmed virological failure on a dolutegravir-based regimen can pose challenges because of uncertainty around whether dolutegravir resistance has actually developed and switching is needed, or whether only interventions to improve adherence without switching are sufficient. These considerations should be addressed to consolidate expected gains from widespread introduction of dolutegravir in low-income and middle-income countries.