Boosted PI

The boosting of PIs is a therapeutic strategy wherein a small dose of ritonavir is given concurrently with another PI to pharmacologically enhance exposure to the latter PI through the inhibition of the enzyme cytochrome p450. For many of the PIs, ritonavir boosting results in improved drug levels that can increase efficacy, decrease pill burden, add flexibility to the dosing schedule, and remove fasting restrictions. However, with increased drug exposure, there is the potential for increased toxicity, which has manifested in greater gastrointestinal intolerance (lopinavir/ritonavir), nephrolithiasis (indinavir), hyperbilirubinemia (indinavir, atazanavir), and hyperlipidemia (many PIs). Boosting can also result in significant drug interactions with other compounds metabolized by the cytochrome p450 pathway. Whether boosting increases lipodystrophy remains unclear.

At this point in time, most PIs -- including lopinavir, saquinavir, indinavir, and amprenavir -- are given in the boosted form. Whether atazanavir should be administered without boosting to antiretroviral-naive patients remains an issue of debate, but it is generally boosted when prescribed for treatment-experienced patients and must be boosted when used in tandem with an NNRTI or tenofovir. Nelfinavir, which is naturally boosted by food, remains the only PI for which boosting with ritonavir is not recommended.

AMH.