For the Poor, High Costs,
R Rigid Regimens Dim
Drug Cocktails' Promise
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A Major Issue for Medicaid

NEW YORK -- As word of a promising new AIDS treatment passes from street corner to street corner in the nation's inner cities, concerns are mounting over who will get the revolutionary drugs -- and who will pay for them.

The new drugs, known as protease inhibitors, have been on the market for just a few months. But, taken in combination with two older medications, they already appear to work far better than any treatment previously devised. In many patients, they are removing all detectable evidence of HIV, the AIDS virus, from the blood, dramatically improving patients' health. More favorable test results are expected to be announced next week at the 11th International Conference on AIDS in Vancouver and to spawn new world-wide interest in the treatments.

But the new three-drug cocktail is enormously expensive: about $12,000 to $16,000 a year at retail, depending on which of several drugs are used. If only half the roughly 800,000 infected Americans eventually receive the new drug therapy, the annual bill could jump to as much as $6 billion a year, making it one of the most costly health programs in the world.

Moreover, benefiting from most versions of the drugs requires meticulous care by the patients. The therapy involves swallowing 14 to 20 pills a day in a rigid dosing schedule, often with strict dietary restrictions that may have to be continued for many years, perhaps for an individual's entire life.

Most worrisome, researchers fear that suspending treatment for even a few days, due to loss of insurance coverage, simple forgetfulness or an episode of narcotics use or crime, may generate dangerous new drug-resistant strains. With AIDS spreading most swiftly among the inner-city poor, particularly intravenous-drug users, just getting people to make proper use of protease inhibitors looms as an enormous -- and, once again, costly -- public-health problem.

At a time of intense focus on the high cost of health care, the new treatments are certain to raise anew the question of how far the nation is willing to go to care for many of its sickest, especially those who live on society's fringes. "Getting the new drugs to those who need it, especially to the inner city where AIDS is growing fastest, is going to be a real test," says William Arnold, who directs a lobbying group pressing Congress to allocate new funds for the protease medicines.

Given all the domestic complications, few U.S. health officials or pharmaceutical-company executives are currently even contemplating the outsized economics of providing the new therapy to the estimated 15 million to 20 million people infected with HIV who live outside the U.S., especially the millions in Africa and Asia where access to long-term medical care is often minimal.

Both the great promise and serious problems generated by the new drugs are already apparent at Harlem Hospital in upper Manhattan. The hospital's crowded AIDS clinic, wedged into a few examining rooms in a corner of the hospital's original 100-year-old red-brick building, is especially hectic and upbeat these days. Its clients, mostly low-income or jobless men and women in their 20s and 30s, are streaming in daily asking about the new drug treatment.

"There's a lot of excitement about the drugs," says Wafaa El-Sadr, director of infectious diseases at the hospital. "It's already changing our patients' attitudes about treatment and what's possible for them."

Yet, given the complexity of taking the medication, Dr. El-Sadr won't prescribe it to everyone. "We have many patients who can and will benefit right now," says Dr. El-Sadr. "But we have many others whose lives are in too much turmoil to prescribe them the therapy. We have patients using illicit drugs, some are homeless, some don't even have enough to eat. It won't be helpful to start them on the medication until their lives are more stable."

Dr. El-Sadr and others say that if these patients stop using the medication, the virus is certain to re-emerge in their bloodstreams, perhaps in versions untreatable by the new medicines. "From a public health point of view, for the larger community, that would be disastrous," Dr. ElSadr says.

Even for people whom Dr. El-Sadr and other AIDS doctors deem eligible for the treatment, securing funding can be complicated. Already there is evidence that U.S. demand for the new drugs is rising rapidly enough to tax existing government programs and some private insurance plans.

"The Clinton administration is committed to getting these drugs to everyone who needs them," says Patricia Fleming, the White House's National AIDS Policy director. But doing so, she acknowledges, won't be easy.

Never before has a major new class of medicines entered the marketplace so quickly. In December, the Food and Drug Administration approved the first of the protease drugs, Hoffmann-La Roche Inc.'s Invirase. Then, in early March, the agency approved two more protease drugs, Merck & Co.'s Crixivan and Abbott Laboratories' Norvir. Since then, more than 60,000 Americans have been prescribed one of the three new drugs, and pharmaceutical-company marketing officials believe that at least 50,000 to 75,000 more people will get the new drugs by year's end.

Immediately after the FDA action in March, and following intense lobbying by several AIDS advocacy groups, President Clinton asked Congress for an emergency infusion of $52 million for the states' AIDS Drug Assistance Programs, or ADAP, a special program created in 1987 for the uninsured.

Though most private insurers and managed-care concerns are currently including protease inhibitors in their coverage, some are restricting reimbursement to people in advanced stages of HIV infection. Moreover, statistics from several state programs suggest the government allocation for the uninsured is far short of what is needed.

This week, for instance, New York is making available $9 million for the protease drugs, its share of the federal grant approved by Congress. But New York's ADAP officials expect that at least 35% of the 10,000 people who currently receive the coverage may soon ask to get the new drugs. This would cost New York between $40 million and $45 million a year. If all the patients eligible for ADAP eventually seek the new therapy, the state's annual bill will reach $120 million, almost as much as the entire federal ADAP program spent in 1995.

Questions are also being raised about the capacity of Medicaid to absorb the cost of protease inhibitors for those it covers. The government health plan for the poor, jointly funded by state and federal taxpayers, currently pays the freight for about half of all AIDS drugs used in the U.S. But in late June, officials at the U.S. Department of Health and Human Services became concerned when several state Medicaid programs began restricting eligibility for the new therapy. As a result of the restrictions, the federal officials dispatched letters to all state Medicaid administrators urging them to reimburse for all three protease drugs, despite the added cost to the states.

"There's no question that doing what's right and covering these drugs is going to be a difficult burden for many of the Medicaid programs," says Eric Goosby, director of HIV policy at Health and Human Services.

For the low-income AIDS patient, the bureaucratic complexities can be numbing. Anna, a 44-year-old widow with advancing AIDS, spent two anxious months this spring trying unsuccessfully to finance the $250-a-week therapy that Dr. El-Sadr had prescribed. Because Anna works, she isn't eligible for Medicaid. Her employer's health-insurance plan, a managed-care provider, doesn't cover antiviral AIDS drugs. And at the time she was seeking treatment, the state ADAP program didn't have sufficient funds to include her.

"I was going crazy," says Anna, who asked that her last name not be used. Finally, a few weeks ago, Merck agreed to give Anna a free supply of its protease drug, Crixivan, as part of a stop-gap giveaway program it and other drug makers are offering to about 5% to 10% of patients using their medications. In recent weeks, Anna's once-deteriorating immune system has stabilized, although it still is relatively weak. "I hope I'm able to keep getting the drugs," she says.

Merck says it is committed to providing drugs to those not covered by an insurance plan who meet certain income requirements. But all the drug makers hope the giveaway programs are temporary safety nets; each company believes the government and employers are ultimately responsible for paying for most people receiving their medicines. The companies point out that they have spent hundreds of millions of dollars developing these drugs, and expensive research is continuing. For now, supplies of the drugs are barely keeping up with the burgeoning demand, and it remains to be seen whether prices will come down as supplies increase and competitive forces intensify.

Ironically, the more attention generated by the new treatments, the tougher it will be for people like Anna to maintain access to the therapy. The Vancouver AIDS conference, in particular, is expected to generate additional publicity. As reported previously in a front-page article in this newspaper, scientists at the AIDS meeting are expected to announce several significant advances. The developments include a report of one test in which 90% of patients who received Merck's Crixivan and two older medicines, Glaxo Wellcome PLC's drugs AZT and 3TC, had no detectable virus in their blood after as much as 48 weeks of use, something no other treatment has achieved.

There will also be a report that 11 of 12 newly infected test patients had no detectable trace of the virus in their blood after eight to 10 months of treatment with Norvir and the two older medicines, generating hope that the new therapy may completely eradicate the virus from people who receive treatment in the earliest stage of infection. At present, no antiviral treatment is offered to people at the beginning of the infection because none has yet shown any long-term impact on the progression of the disease.

Another factor expected to increase interest in the drugs is the recent release of a new test that can measure the precise amount of virus circulating in a person's blood and thus chart the impact of the new drugs.

"It's amazing how many patients are coming in and asking to have their viral load tested," says Charles Farthing, an AIDS physician who treats a large pool of low-income patients in Los Angeles. "Having a test that can monitor how well the drugs are working in reducing virus levels is absolutely certain to spur an even greater interest in using the new drugs."

Willie, a 39-year-old Harlem resident recovering from addictions to cocaine and heroin, was recently released after a three-year stint in New York's Rikers Island prison. He says he learned about the protease drugs from a film he was shown at a community drug-rehabilitation program and also from a friend.

His friend's viral load improved dramatically "in just a few weeks," says Willie, who asked that his last name not be used because his family doesn't know he is infected with the AIDS virus. "That really, really reinforced my desire to use the protease drugs right now. I'm not sick and I don't ever want to get sick."

Several days later, Willie asked for and received the drugs from an AIDS clinic he uses in downtown Manhattan. The treatment was paid for by Medicaid. Does he think he can continue taking 17 pills a day forever? "Well," he says, "I'm going to try my best."

Others are skeptical about how the protease inhibitors will fare on the street, as opposed to in test conditions or among well-heeled patients. Sheldon Julius, HIV-positive and recovering from almost 30 years of drug addiction, spends his days talking about the new medicines to men and women as part of volunteer work he does for Harlem Hospital's AIDS clinic. "A lot of people are saying they've heard something about this new kind of medicine that's different, more powerful, that's not like AZT," Mr. Julius says. "But I tell them, `If you want the medicine, you first gotta clean up your act.'"

Mr. Julius says he recently was "deeply disturbed" when a longtime friend of his sold a street "drug broker" her new supply of protease medicines and other drugs for $75, apparently so she could buy some narcotics. "I know if we work hard to get people these drugs, they've got to be responsible about using them right," Mr. Julius says. "My job is to make certain people understand that you can't take these drugs lightly."

Still, Steven Deeks, a physician at San Francisco General Hospital, says he is worried that even if patients get the drugs, they may quit using them abruptly because of side effects. Dr. Deeks notes that one of the drugs, Abbott's Norvir, can cause nausea and headaches during the first few weeks of treatment that are so serious "that a good number of my patients simply stopped taking the drugs." (Abbott says the side effects can be handled by using a lower dose at first.)

Adds Dr. Deeks: "The great results being reported are from tightly controlled clinical trials. I'm worried when these drugs get out into the community. People are going to have a lot of problems using them."

Dr. El-Sadr at Harlem Hospital's AIDS clinic believes her medical center's success in treating tuberculosis may serve as a model for what's needed to make proper use of the new drugs. TB can be cured with a three-drug regimen. Under Dr. El-Sadr's direction, the hospital has created a program in which TB patients receive their medication under "direct observation" of health-care workers at the hospital's clinic.

As an incentive, patients receive subway tokens and free certificates to McDonald's. As importantly, Dr. El-Sadr says, the clinic tries to provide a nurturing atmosphere for "people who often have no one else to turn to," celebrating their birthdays at the clinic and taking them on outings. All of this is funded by state and city agencies seeking to avoid the spread of drug-resistant TB if patients stop taking their medicine.

TB can be treated with drugs taken just three times a week for nine months, and the medicines cost a tiny fraction of what the new AIDS drugs cost. Still, says Dr. El-Sadr, "in an ideal world, it's exactly the kind of program we'd put in place for AIDS."