Checking the Status: The Evolutionary Explanations and Drug Resistance Prevalence to Dolutegravir for HIV Treatment (A Review)

Abstract

Drug treatment advancements for HIV have dramatically advanced since the virus’ identification in the early 1980s. Integrase strand transfer inhibitors (INSTIs) are one of seven HIV treatment drug classes currently utilized to create an undetectable viral count in blood samples of people living with HIV (PLWH). First generation INSTIs are documented with low barriers of genetic resistance, which indicates that the number of mutations to lead to a drug resistant mutation is low. The introduction of dolutegravir, a second generation INSTI, shows a higher barrier of genetic resistance that will reduce drug resistant mutations to INSTIs and increase the overall effectiveness of this class of HIV treatment. PLWH can be categorized based on whether they received treatment previously/currently or have never received treatment. Therapy naive and previously treated (successfully or unsuccessfully) patients for HIV report different rates of drug resistant mutations compared to actual resistance to dolutegravir, 0.4-31% and 0.1-67.2% respectively. Evolutionary considerations of genetic resistance, including epistatic interactions and point mutations, suggest both non-polymorphic and polymorphic mutations for these drug resistant mutations. An incomplete understanding of how evolutionary factors contribute to HIV drug resistance highlights the importance of conducting further research. This research may help improve the efficacy of second generation INSTIs in future treatment options for PLWH. This review describes the landscape of existing research on drug resistance prevalence for dolutegravir and possible evolutionary explanations on how these mutations arise in the first place, leading to implications in developing more robust treatment modalities.