When Do Minority Drug‐Resistant HIV‐1 Variants Have a Major Clinical Impact?

As our understanding of the virologic and clinical significance of drug-resistant human immunodeficiency virus type 1 (HIV-1) continues to expand, attention is now turning to detecting and assessing the clinical impact of minority (low frequency/abundance) drug-resistant HIV-1, the variants in the viral population present below the ∼20% detection threshold of conventional bulk sequencing. The interest in studying minority resistance has been fueled by improved diagnostic technologies that allow detection of drug-resistant variants below the 1% threshold, and by the recognition that drug-resistant viral populations often exist as a complex mixture of genetic populations in which only the dominant viral sequence is detected by standard sequencing. Three common approaches are used to detect minority resistance: point mutations assays, clonal sequencing, and ultra deep se-