Protease Inhibitor Therapy: Boosted and Double-Boosted Options to the Fore

in april 1999, dr. schlomo staszewski had a simple message for clinicians attending his first prn lecture: that protease inhibitors were a less-than-ideal therapeutic option and that focus should be placed on prescribing protease inhibitor-sparing regimens, whenever possible. “We were seeing problems with dosing, with side effects, with dietary restrictions, with resistance and cross resistance,” Dr. Staszewski said upon returning to prn in November 2003. “For these and other reasons, I tried to explain that we shouldn’t be using protease inhibitors anymore. I don’t want to be viewed as an opportunistic guy, that I change my opinions every time I get up to talk. But times have changed and our patients have changed. There’s a new perception of protease inhibitors and we’re seeing that these drugs can now be used more effectively than when they were first approved.” Protease inhibitors remain an extremely valuable therapeutic option. There is certainly no shortage of data indicating that protease inhibitors have played an enormous role in decreasing mortality and morbidity while at the same time significantly enhancing the overall quality of life of most people living with the virus. However, protease inhibitors also have several disadvantages, all of which have been well documented. First, protease inhibitor therapy often comes with a high pill burden, complex dosing schedules, and careful dietary considerations. Second, they are associated with a growing number of shortand long-term side effects, including diabetes and other metabolic complications. In turn, a snowball effect can ensue: Each of these potential drawbacks has been associated with nonadherence, which can ultimately cause resistance and cross-resistance, virologic failure, lack of therapeutic options, and disease progression. However, a great deal of data generated over the past several years have brought about a sea change in the way these drugs are used. Pharmacokinetic “boosting”—the use of ritonavir (Norvir) to boost concentrations of other protease inhibitors—has, in effect, rendered many of these drugs easier to take and more effective. Research is also emerging regarding the use of two protease inhibitors—both boosted using low-dose ritonavir—as a therapeutic option, which appears to hold promise, particularly for patients who have tried and failed protease inhibitor therapy in the past.