In the presence of RTV, the metabolism of concomitantly administered PIs by the cytochrome P450 3A4 (CYP3A4) isoenzyme is inhibited; higher plasma and tissue drug levels are maintained with less variability. The enhanced pharmacokinetics result in prolonged suppression of viral replication including strains with moderate phenotypic resistance leading to improved therapeutic outcomes. RTV enhanced dual PI therapy offers additional advantages as combinations of PIs with different and non-overlapping mutation patterns would be expected to delay emergence of viral resistance, coupled with the notion that the selection of resistance to two or more agents may require a greater number of mutations than that required to overcome a single PI. Furthermore, these combination regimens often result in reduction in pill burden, food restrictions, and may be associated with more tolerable side effect profiles.