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From Grapefruit Juice to Ritonavir
What's New, from the 8th Conference on Retroviruses and Opportunistic Infections

March 15, 2001

When the first protease inhibitor (PI) -- saquinavir (Invirase) -- was released in the mid-1990s, people with HIV/AIDS (PHAs) had to take a handful of pills three times daily. Despite taking all those pills, levels of saquinavir in the blood were relatively low. To raise saquinavir levels, the drug's manufacturer, Hoffman-La Roche, suggested that people drink grapefruit juice when they take their drugs. This is because chemicals in grapefruit interfere with enzymes in the digestive tract and liver that would normally break down saquinavir (and other PIs). However, although drinking grapefruit juice did help to raise saquinavir levels, the levels of the drug in the blood still remained relatively low. So Roche started to make a new version of saquinavir, called Fortovase, that is better absorbed. Until the arrival of Fortovase in the late 1990s, researchers conducted experiments to find more effective means than drinking grapefruit juice to boost levels of saquinavir in the blood.

Doctors at Ottawa General Hospital began testing a combination of saquinavir and the PI ritonavir (Norvir). They found that ritonavir not only raises levels of saquinavir in the blood, but that these levels remains elevated for prolonged periods. This means that people only needed to take their drugs twice daily, as opposed to three times a day. Based on the PI-boosting effect of ritonavir, more doctors are using that drug to boost levels of others PIs, including the following:

The advantage of using ritonavir is that it not only raises levels of the other PIs used in a drug combination, but it also helps maintain those levels -- to the point where researchers are now testing once-daily regimens of ritonavir with other PIs such as indinavir and amprenavir.

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