Global Policy Forum

By Donald G. McNeil Jr.

Contradicting long-held prejudices that have clouded the campaign to bring AIDS drugs to millions of people in Africa, evidence is emerging that AIDS patients there are better at following their pill regimens than Americans are.

Some doctors, politicians and pharmaceutical executives have argued that it is unsafe to send millions of doses of antiretroviral drugs to Africa, for fear that incomplete pill-taking will speed the mutation of drug-resistant strains that could spread around the world. The danger already exists: nearly 10 percent of all new H.I.V. infections in Europe are resistant to at least one drug.

For Africa, the issue is particularly touchy because it is tinged with racism. In 2001, for example there was an outcry when the director of the United States Agency for International Development said that AIDS drugs "wouldn't work" in Africa because many Africans don't use clocks and "don't know what Western time is."

Now surveys done in Botswana, Uganda, Senegal and South Africa have found that on average, AIDS patients take about 90 percent of their medicine. The average figure in the United States is 70 percent, and it is worse among subgroups like the homeless and drug abusers.

Compliance has become easier because drugmakers from India and elsewhere are beginning to make triple-therapy cocktails that come in as few as two pills a day. (These are not available in the United States yet because of patent problems — no Western company makes all three drugs for an ideal cocktail.)

After nearly a decade of watching Africans die because AIDS drugs cost $10,000 or more a year per patient, rich nations began pledging aid after generic competition in 2001 drove prices down to about $300 a year. Last week the World Trade Organization agreed to alter its rules to give poor nations more access to life saving medicines.

But as with any epidemic moving through a poor and ill-educated populace, the threat of disaster clings like a shroud. Patients in badly supervised programs have been caught selling pills or sharing with desperate relatives — acts of greed or mercy that could lead to doomsday strains of the virus. Anti-retroviral therapy "is the No. 1 priority for the developing world," said Robert C. Gallo, director of the Institute for Human Virology and a pioneer in researching H.I.V., the virus that causes AIDS. "But it will be a tragic mistake if it's not done right. You'll have ‘Eureka!' and ‘Thank you, America!' for two or three years — but then you'll get multi-drug resistance, and whoops. . . ."

Drug-resistant strains are inevitable, doctors say, and turn up in every illness from malaria in Africa to children's ear infections in Manhattan. Hard-to-cure variants evolve spontaneously in response to drugs. But they are more likely to grow and be passed on if patients skip doses, because triple therapy often suppresses even mutant strains. To avoid an epidemic of incurable AIDS, new drugs must be discovered faster than old ones become useless.

Africa can still do better than the West, they say, by avoiding old mistakes. Today's drugs are more potent and no one will spend years on one drug, thereby breeding resistance, as many Westerners did on AZT before triple therapy emerged in 1996.

Moreover, doctors say, most African patients are zealous about their regimens. They are also more truthful when estimating their adherence, said Dr. David Bangsberg, a professor of medicine at the University of California in San Francisco who has studied compliance patterns here and abroad. On average, he said, American patients tell their doctors that they are doing 20 percentage points better than they really are — that is, a patient who says he takes 90 percent of his pills will, when tested with unannounced home pill counts or electronic pill-bottle caps, turn out to be taking 70 percent. A study of 29 Ugandan patients found that, on average, they estimated that they were taking 93 percent of pills and proved to be taking 91 percent.

Though poor, more than 80 percent of the Ugandans had jobs, though most earned less than $50 a month. Most were women in their 30's, and paying $27 a month for their twice-a-day, three-drugs-in-one pill called Triomune, made by Cipla Ltd. of Bombay.

In many such cases, explained Dr. Merle A. Sande, a University of Utah medical school professor who also works in Uganda, the whole extended family, possibly with several infected members, will chip in so that one member will be saved to care for the children. "If the whole family is pooling its resources to pay for you," he said, "you damn well better take your drugs. "That's a whole different scenario from the U.S., where patients get free medicine, and if they change therapy, will let a month's worth go to waste."

Several doctors in Africa said their patients were highly motivated because they had seen friends or family die. Most come in only when deathly ill, so the drugs seem to perform a miracle, making them well enough to go back to work. And even $1 a day is a lot, so they treat it as "an investment," said Dr. Elly Katabira of Makerere University Medical School in Uganda.

In Botswana, with the world's highest infection rate, pill counts on 400 of the 10,000 patients on therapy showed that 85 percent were taking their pills flawlessly, said Dr. Ernest Darkoh, the national program manager. "If you loosen the criteria a little — missing a dose by two hours, for example — you get about 90 percent," he added. There are a few exceptions, he admitted: "Some people bring back their pill containers saying, `Thank you, but my traditional healer told me not to take these.' "

However, some programs are not as good as others. In Nigeria, Africa's most populous country, an ambitious, widely praised plan to get generic drugs to 15,000 citizens has been hampered by bureaucracy, corruption and a scarcity of laboratories. Dr. Ernest Ekong, an AIDS specialist at the Military Reference Hospital in Lagos who has made Nigeria's case at international conferences, at first said adherence so far has been "no problem." Then he began to qualify that. Some patients, he said, have felt so well that they shared pills with friends who could afford the $10 monthly charge. Some who developed "nevirapine rash," or nerve tingling, cut back. "And," he admitted, "a very small percentage are selling their drugs." Non-adherence, he said, is worst among patients with co-infections that require more pills — tuberculosis patients, for example, must also take four antibiotics.

No formal resistance study has been done, but Nigerian doctors are worried about a few patients who are taking all their pills but not getting better — a sign that they might have resistant strains. The best adherence seems to come under tight supervision. A recent study in Cape Town found that older patients, patients who took pills twice a day instead of three times, and patients who spoke the same language as clinic staff members tended to do best. In May 2001, Africa's best-known pilot project was opened by Doctors Without Borders in a crowded, dirt-poor black township near Cape Town called Khayelitsha.

Because the drugs were then scarce, the charity set high hurdles for patients, so high that only 550 of the clinic's 5,000 visitors are taking medication now. It reports extraordinarily high levels of compliance. Pill counts by social workers show that, after six months on treatment, 96 percent of the patients are still taking 95 percent of their pills.

As a surer but more expensive backup, blood tests see how many have minuscule levels of virus, an indication that they have faithfully taken their pills. After six months, 91 percent do; at 18 months, 83 percent do. "That's pretty good," said Dr. Eric Goemaere, the program's director. "Certainly better than what you see in most North American studies."

To qualify for treatment, patients must give up all alcohol and drugs; complete three months of taking a simple antibiotic; be on time for four clinic appointments in a row; reveal to their families that they are H.I.V. positive; and choose a friend who must come to counseling, make sure all pills are taken and report problems to a nurse. Dr. Bangsberg expressed surprise at how demanding the clinic was. "Imagine trying to impose the no-drinking rule in San Francisco," he said.

Such standards are tough but necessary, Dr. Goemaere said. Binge drinking is the norm in South African townships, he said, and studies show that patients with histories of alcohol abuse or depression are the worst at taking their pills. "There are certainly parts of Africa where you wouldn't want to try this — in Congo, for example," he said. "But 65 percent of South Africa is urbanized. People know how to take a taxi and get to an appointment — and how to take their pills."

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