The War For Drugs

RIETPOORT FARM, STANDERTON DISTRICT, SOUTH AFRICA—Every time Christina Makhubu came home, it was like Christmas. Working as a housemaid in South Africa’s capital, Pretoria, she made more than anyone else in her family, including her brothers, who work as farmhands. So she would bring her mother dresses, her two sons books and once even a bicycle, school fees for her nephew, furniture for the house, and of course food for everyone. Her family—three generations gathered together in a room lit by a single candle, around the table where they would feast at her homecomings—remembers the last time Christina came home. She was so tired, and then the headaches began. She said she felt drunk and confused, and then she started seeing things that weren’t there—snakes on the wall, and other animals that terrified her. The pain in her head just got worse, and when she began to fall down trying to walk, they took her to the hospital for the last time.

At some point, maybe years before, Christina had inhaled spores of the cryptococcus fungus. Healthy people control the infection, but HIV had ravaged Christina’s immune system, so the fungus was able to pass into the blood, which carries it to the brain. There it sets up colonies—pearly, glistening spheres along the blood vessels of the brain, most abundant on the wrinkled surface but also present deep in the brain’s core. The fungus does not kill neural cells, but it makes them swell, squeezing the brain inside the skull and turning the gray matter into “a big bag of mush,” explains John Bennett, who has studied the disease for 30 years at the National Institute of Allergy and Infectious Diseases in the United States. “When the skull is cut open at autopsy, the brain bulges out like toothpaste out of a tube.”

This is cryptococcal meningitis, one of the most feared opportunistic illnesses that kill people with AIDS. It can be treated, but one of the key drugs—fluconazole, which also works well against thrush, an extremely common ailment among HIV patients—costs the equivalent of about $7.50 for a standard dose, far too much for South Africa’s struggling health care system. Pharmaceutical giant Pfizer holds the patent for fluconazole and sets the price in almost every country. But in Thailand, the government permits local companies to make a generic form of the drug; the price for the same dose is only about 70 cents.

Now, the Nobel Prize-winning organization Médecins Sans Frontières, ACT UP, and a South African AIDS activist group called Treatment Action Campaign are leading an effort to pressure Pfizer to match the Thai price, or to give TAC a license so that it can find a company to manufacture a generic version of the drug. Last Monday, the activists delivered letters to Pfizer offices in 18 different countries, giving the maker of Viagra and Zoloft one week to agree. But on Monday, the deadline passed and the company did not acquiesce, so both sides are preparing for a long siege.

This high-profile, high-stakes battle raises the possibility that the South African government might compel Pfizer to allow a generic version of fluconazole to be manufactured. Or the government could pull an end run by importing the Thai version of the drug. Either of these actions would force a showdown on international trade regulations, which the pharmaceutical industry insists support the right of companies to determine prices around the world. But humanitarian groups—as well as a swelling chorus of politicians, including Clinton, Gore, and many members of Congress—believe those regulations should allow developing countries to obtain medicines that fight major epidemics, such as AIDS, at the lowest possible price.

This is the fight that will capture the attention of the international media. But here in South Africa, which is a blend of the First and Third Worlds, the push for this drug has laid bare some of the most daunting problems in treating AIDS. Insufficient money to purchase medicines is certainly the biggest obstacle, but there is also the government’s frequent failure to deliver cheap drugs to hospitals, doctors’ unfamiliarity with treatment possibilities, and a population that thinks of HIV as utterly hopeless and so gives in to despair. The fight over this one drug—which does not even target HIV itself but rather some of the opportunistic illnesses the virus causes—is therefore a microcosm of South Africa’s battle to treat its 3.6 million citizens with HIV.

At Standerton Provincial Hospital, where Christina Makhubu died, senior medical superintendent Eckhart Oosterhuis desperately wants fluconazole, but he also wants a lot of other drugs. In 1998, the last year for which local figures are available, a shocking 51 percent of women attending public prenatal clinics in Standerton were infected with HIV. The hospital is supposed to stock 169 so-called essential drugs, but, producing a list, Oosterhuis says he is completely out of 38. “Our supplies are low for about another 50,” he adds.

In AIDS, there are two conditions that are absolutely critical to treat: tuberculosis, because it probably kills more HIV-positive South Africans than any other opportunistic infection and because it imperils the general population; and sexually transmitted diseases, because people who have them are more likely to contract and transmit HIV. But despite being fairly cheap, drugs to treat these problems are often unavailable. For example, according to a report by the provincial government, TB drugs were out of stock between 15 and 30 percent of the time. As for STD drugs, Rensie Vellema, the Standerton district communicable disease coordinator, says that at least one is unavailable most of the time. “It’s really a disgrace,” she says. “If we send patients to a private pharmacy, they can’t afford the drugs.”

Mpumalanga Province is “worse than the norm,” says Andy Gray, an expert on drug availability in South Africa with the independent organization Health Systems Trust. But he adds that in rural clinics around the country, drug shortages “are not uncommon.” Here in Mpumalanga, the province with the second-highest rate of HIV in South Africa, Kelvin Billingurst, the chief medical officer in charge of AIDS, says, “If we can’t have drugs for TB and STDs, then we can’t even begin to think about fluconazole.”

“That is a bureaucrat’s viewpoint,” says Zackie Achmat, one of the founders of TAC and an architect of the current Pfizer battle. “It’s their administration that is bad.” He hopes that by pushing for fluconazole, the larger problems of the health care system will come into focus—and under pressure.

Achmat also hopes something else will become clear: the fact that there are life-prolonging treatments. He points out that the government has not yet issued national treatment guidelines and says that for many opportunistic illnesses, “The line is, very quietly, ‘Don’t treat.’ ”

Certainly that is true for cryptococcal meningitis. A few large hospitals do treat this disease, but most medical centers are more like Natalspruit Hospital, serving three teeming, crime-ridden townships outside of Johannesburg. Here, the most common problem is not HIV but trauma—injuries from violence, car crashes, and the like. When HIV patients arrive with cryptococcal meningitis, they are stabilized, given painkillers for the headache, and sent home to die.

After their inpatient rounds, where virtually every bed is full, and after their outpatient clinic, where scores of impoverished people wait on wooden benches, Drs. Leena Thomas and Florence Tleane discuss fluconazole. They want the government to get the best price, but they are caught in devil’s dilemmas that American doctors rarely face.

For example, patients with cryptococcal meningitis usually need to be hospitalized for two to four weeks, “but a long stay means taking up someone else’s bed,” says Thomas. The death rate from cryptococcal meningitis “is quite high despite treatment,” notes her boss, medical superintendent Varughese George. “So, should we treat a disease that has a poor outcome or utilize those funds for other patients?”

Tleane says she would refer cryptococcal meningitis patients who are HIV-negative to a better-equipped hospital, because such people stand a good chance of being permanently cured. But in an AIDS patient, the disease is a sign that the immune system is so tattered that the end is not far off. Moreover, to keep the disease from recurring, HIV patients must take fluconazole every day for the rest of their lives. In addition to cost, “compliance is a problem with our patients,” says Thomas. “Would they take the pills? I can’t say that I’m desperate for this drug. I haven’t used it on patients, so I can’t say how effective it is in our community,” she concludes.

“You’re not going to see enthusiasm in doctors who haven’t treated people with the drug—not because they don’t care but because they don’t know,” says Achmat, who has HIV himself. “This shows the amount of work we have to do in this country. Treatment literacy, even among doctors, is very bad.”

It’s worse, of course, among patients. “Since there are no treatments, people are always hopeless,” says Selby Sibaya, an openly HIV-positive counselor at Standerton hospital. His colleague, chief nurse Evelyn Moumkawe, agrees. “The minute they know they’re positive, they deteriorate fast,” she says. “It’s psychological. They despair.”

Ultimately, this is what the fluconazole campaign is trying to do—inject hope into the bleakest of epidemics. That’s more than a sentimental gesture. People avoid getting tested, say doctors and AIDS workers, because what can they do if they’re infected? And if they don’t know they carry the virus, they often are not as careful about protecting their partners. If parents could live an extra year or two—which has been proven possible even without drugs that target HIV itself—their children might get a better start in life before being orphaned. Drugs like fluconazole would inspire hope, says Sibaya, “because we wouldn’t be saying anymore, ‘Go home and wait for your time.’ ”

Just a few steps away from Sibaya’s office, a woman lies panting, even though she is breathing through an oxygen mask. TB is rampant in her lungs, complicated by thrush, a fungal infection that has coated her mouth and esophagus with a white, velvety carpet of pain. More than 40 percent of South African HIV patients get thrush. The woman panting into her mask has it so bad that she can’t swallow, not even to drink, yet the disease also gives her diarrhea, depriving her of nutrients and energy. She’s being fed intravenously, but if she could eat solid food and didn’t have to fight two major diseases at once, she’d have a much better chance of pulling through.

The drug she’s been given for thrush, nystatin, is weak and hasn’t worked. Fluconazole is the most effective drug, but of course it’s not available. And so, says nurse Moumkawe, “she probably won’t make it.”

Additional articles on AIDS by Mark Schoofs.