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.
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.
