Mutations in the HIV-1 3′-Polypurine Tract and Integrase Strand Transfer Inhibitor Resistance
Yuliang Wei, Nicolas Sluis‐Cremer
Abstract
Integrase strand transfer inhibitors (INSTIs), in combination with other antivirals, are widely used for the treatment of HIV-1-infected individuals. HIV-1 resistance to INSTIs is typically associated with mutations in the viral integrase gene (1). However, recent studies suggested that mutations in the HIV-1 3′-polypurine tract (3′-PPT) may also confer viral resistance to INSTIs. Specifically, Malet et al. (2) reported in an in vitro selection experiment that a high concentration of dolutegravir (DTG) selected for mutations in the 3′-PPT that conferred INSTI resistance. Wijting et al. (3) reported on the selection of mutations in the 3′-PPT, but not integrase gene, in the virus from an infected individual who failed DTG maintenance monotherapy. However, no follow-up studies have ascertained whether the 3′-PPT mutations reported by Wijting et al. reduce INSTI sensitivity in phenotypic analyses of drug resistance. The primary objective of this study was to address this critical knowledge gap.