Protease inhibitor double boosting

Concepts in medicine sometimes cycle in and out of favour. Occasionally, something with a new name sounds novel but in fact may reflect an old idea, and every so often a practice adopted for one reason turns out to be useful for an entirely different rationale. The current trend toward combining multiple protease inhibitors (PIs) reflects these themes.

Central to these efforts has been Kaletra, the fixed combination of lopinavir and low-dose ritonavir, which opens the possibility of boosting another PI at the same time, usually saquinavir or amprenavir. In patients in whom initial regimens containing indinavir or nelfinavir fail, the addition of one of these agents to Kaletra seemed potentially useful because the key resistance mutations associated with these drugs were often absent.

Since the 100 mg of ritonavir contained in a standard dose of Kaletra could boost the levels of either amprenavir or saquinavir when used without lopinavir, the same effect was expected when the three agents were given together.