The pros and cons of protease inhibitors
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.
Though the drugs have shown great promise, nobody knows how long their effectiveness will last or, in some cases, if taking one protease inhibitor will make a person resistant to another. What many researchers fear is mounting evidence that the slightest deviation from the prescribed regimen of any of these difficult-to-take drugs can create a resistant viral strain, rendering a particular protease inhibitor ineffectual--and perhaps even more deadly. 'Deviating for more than an hour from the regimen gives a slight edge to the onset of resistance to Crixivan,' Kuromiya says. People with resistant strains could then transmit them to others, eventually creating an entire population that won't respond to protease inhibitors.
Barbara Zeller, medical director of Project Samaritan in New York City, points to the outbreak of drug-resistant tuberculosis a few years ago. 'This problem emerged over 20 years of taking anti-tuberculosis drugs incorrectly,' she says. 'Given our knowledge of how fast HIV mutates, the potential for a resistant epidemic is real.' Merck is so concerned that people won't take its drug properly that it sells Crixivan through a single distributor, Stadtlander's Pharmacy, enabling it to monitor compliance.
Some believe this threat is overblown. 'There's not enough evidence of resistant virus to suggest panic at this point,' says Linda Grinberg, a PWA and president of the National Endowment for AIDS Research. 'But until people with AIDS are ready to commit to a strict regimen, they should not start protease therapy.'
Considering how expensive the new therapies are--especially since they're usually prescribed in triple-drug combinations--sticking to a strict regimen seems like a luxurious concern. Almost half of all people with AIDS are on Medicaid. Thousands more make too much money to qualify but can't afford health insurance; the federally funded AIDS Drug Assistance Program (ADAP) reimburses these people for the cost of prescriptions. Each state, however, determines which drugs and how many it can afford to cover.
Presidential politics isn't helping. When Congress and President Clinton ended welfare as we know it, they also knocked tens of thousands of people with HIV off Medicaid as well. And Bob Dole wants to scale back welfare even more. 'Regardless of who ends up in office, additional cuts or limitations on Medicaid would have serious consequences for people with AIDS,' says Jeff Bloom of AIDS Action Council, a Washington-based lobbying group. 'We don't have the luxury of playing yo-yo with protease inhibitors. Once you start them, you need to take them correctly.'
Dole's campaign wouldn't respond to requests to elaborate on his health care agenda. Clinton did issue an executive order giving ADAP programs an additional $52 million, and he's promising that if he's re-elected he'll pass a law reinstating Medicaid benefits to many who've lost them. 'The President and this Administration are committed to making sure that as many PWAs have access to protease inhibitors as possible,' says Richard Sorian, spokesperson for the White House Office of AIDS Policy. 'In June, the President increased his request for the $52 million spent this year to $117 million for 1997 fiscal year. And the Senate subcommittee has voted to approve all $117 million earmarked specifically for ADAP programs. The total federal funds committed for 1997 is now $195 million.'
None of this helps Dick Scanlan make his decision about whether to start protease therapy. Like so many, solvent or poor, he wants the drugs' benefits, but not the kidney-stone attacks or intermittent weeks of nausea. Then there's the danger of missing a dose. Scanlan could live without the anxiety that an impromptu night at the theater might render a potentially life-extending therapy useless.
But there's an upside to Scanlan's dilemma. While we haven't found a cure yet, we have finally managed to almost completely suppress the virus--if only for a while. At last, it's the beginning of the end.