Role of phenotypic investigation in the era of routine genotypic HIV-1 drug resistance testing

The emergence of drug resistance can seriously compromise HIV type-1 therapy and decrease therapeutic options. Resistance testing is highly recommended to guide treatment decisions and drug activity can be accurately predicted in the clinical setting through genotypic assays. While phenotypic systems are not suitable for monitoring drug resistance in routine laboratory practice, genotyping can misclassify unusual or complex mutational patterns, particularly with recently approved antivirals. In addition, phenotypic assays remain fundamental for characterizing candidate antiretroviral compounds. This review aims to discuss how phenotypic assays contributed to and still play a role in understanding the mechanisms of resistance of both licensed and investigational HIV type-1 inhibitors.