Curse or Cure?

The pros and cons of protease inhibitors

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Hailed as a 'cure' for AIDS and the 'best ever' defense in the fight against HIV, protease inhibitors seem to offer a glimmer of hope for thousands of people living under an AIDS-imposed death sentence. But these new drugs could turn out to be problematic. If they aren't taken properly--either stopping therapy once it's begun, taking a lower dose than suggested, or simply forgetting to take the nightly pill--HIV could quickly develop resistance, rendering the drug useless and patients worse off than before.

That's why Dick Scanlan, a New York City writer with AIDS, hasn't rushed to jump on the protease bandwagon. 'My concern is that once again we're going to be heartbroken,' Scanlan says. 'Hope is the most painful emotion, because hope is responsible for disappointment. That's why I think people with AIDS [PWAs] aren't breaking open the champagne.' Scanlan's doctor agrees, and so they are waiting. But many PWAs with no other options face a decision that Scanlan's good health permits him to delay.

Here's how the new drug works: A virus can't reproduce on its own, so it invades a cell, kicks out the native DNA, and inserts its own, turning that cell into a factory of viral reproduction. For the factory to manufacture properly, though, HIV has to chop itself into smaller pieces. An enzyme called protease acts as the guillotine; a protease inhibitor seals the guillotine shut, and the factory starts creating a defective product. Drugs like AZT, on the other hand, try to stop HIV from entering the cell's nucleus in the first place. Combining protease inhibitors with the AZT class of drugs works best, attacking the virus in two different ways.

The FDA has approved three protease inhibitors. Hoffmann-La Roche's saquinavir (the brand name is Invirase) was the first out of the gate. Saquinavir has the fewest side effects but is difficult for the body to absorb--and it must be taken three times a day on a full stomach after a fatty meal. A year's treatment costs about $6,865.

By contrast, Merck & Co.'s indinavir, better known as Crixivan, is the protease inhibitor of choice. It brings the amount of 'virus in the blood' down to undetectable levels in a majority of patients--a reason for all of the 'cure' headlines. But common side effects include nausea and diarrhea. It must be taken three times daily at eight-hour intervals on a very empty stomach and costs about $5,640 annually.



Abbott Pharmaceuticals' ritonavir, sold under the brand name Norvir, is also very potent and needs to be taken only twice daily. But the drug must be refrigerated at all times. 'It's hard to take unless you have a portable cooler,' says PWA treatment activist Kiyoshi Kuromiya. The annual cost is roughly $7,480.

A fourth protease inhibitor, Agouron Pharmaceuticals' nelfinavir, brand name Viracept, is due for FDA approval by the end of the year.