The Benefits of Boosting

Interactions between antiretroviral medications are not always a bad thing. In the case of ritonavir, the drug's unique interaction profile allows it to be used to "boost," or increase, blood concentrations of other PIs. Ritonavir works well as a pharmacological enhancer because it inhibits both the initial stages of PI metabolism in the intestines and CYP3A4 processing in the liver.

This capacity has given ritonavir a new lease on life as a low-dose (typically 100 mg) adjunct drug. At the same time, use of full-dose ritonavir has fallen out of favor because its propensity to raise levels of so many medications is more often harmful than beneficial. Low-dose ritonavir has also boosted the fortunes of other first-generation PIs (namely indinavir and saquinavir) by dramatically reducing their high pill burdens, loosening food requirements, and allowing them to be taken fewer times per day.

Today's experimental PI candidates are routinely tested in conjunction with ritonavir. Abbott hit the jackpot with Kaletra, a combination pill containing lopinavir (a second-generation PI) plus a small dose of ritonavir. But the company raised the ire of the HIV community when it increased the price of low-dose ritonavir by 400% in December 2003 -- an attempt, some charged, to give Kaletra a price edge over other PIs.

Researchers are avidly searching for other drugs that can also be used as pharmacological boosters. A few of the approved PIs -- including nelfinavir, which has an interaction profile somewhat similar to that of ritonavir -- have been linked to increased concentrations of other PIs in some studies. But to date none has demonstrated a strong enough or consistent enough effect to give ritonavir a run for its money.