Haste makes waste

When President Bush in 2003 announced a five-year, $15 billion plan to fight AIDS in developing countries, supporters saw it as a giant step in putting the "compassionate" back in "compassionate conservatism."

Apparently, the 1,000 or so protesters gathered outside the July 12 opening session of the International AIDS Conference missed the memo. "Access Denied to All," read their pink T-shirts, an ironic twist to the official title of the conference, "Access for All." Many carried anti-American banners and posters, including an oversized photo of George W. Bush, spattered with red ink and stamped with the caption "Wanted: AIDS Accomplice."

"We're sick of bilateral donors such as the U.S. who give money with strings attached," said protest organizer Asia Russell of Health GAP, a patients'-rights organization based in San Francisco. Though U.S. taxpayers contribute more money to the international AIDS fight than all other governments in the rest of the world combined, Health GAP and similar groups fault the Bush administration for wanting to have a say in how those funds are spent.

Two policies, in particular, are drawing the ire of activists gathered in Bangkok. First, the White House wants to see American dollars used to promote abstinence, not simply provide free condoms. That's anathema to many AIDS groups, which view abstinence education as a plot hatched by American Christians.

"It appears that this is naked pandering to an extremist constituency," charged Steven Sinding, director general of the International Planned Parenthood Federation. "Millions of people around the world have been persuaded by the arguments of the U.S. government and religious right. Their actions represent a setback in bringing HIV/AIDS under control."

Rather than a setback, however, Ugandan President Yoweri Museveni told the Bangkok conferees that emphasizing abstinence has been key to his country's success in fighting AIDS. "I look at condoms as an improvisation, not a solution," said President Museveni, who saw the infection rate plummet from 30 percent to 6 percent following the nationwide rollout of an ABC program (Abstinence -- Being faithful -- Condoms only as a last resort).

Besides the condom controversy, AIDS activists criticize the administration's go-slow policy on using generic drugs to fight the disease in poor countries. Though the World Health Organization (WHO) has a list of approved "combination" drugs -- generic knock-offs that combine multiple, patented medications in a single pill -- the White House wants the Food and Drug Administration to assess the drugs for quality before shipping them to target countries. In May, the FDA said it would review applications for approval within six weeks -- quite a feat for an agency that usually takes at least six months.

AIDS activists charge the president is dragging his feet to protect the R&D investment of American drug companies, but the administration insists it's concerned about efficacy, not economics.

"If we make a mistake in our little practice of 100 people, 100 people will be hurt," said Joseph O'Neill, Mr. Bush's deputy global AIDS coordinator, speaking at the annual meeting of the Presidential Advisory Council on HIV and AIDS. "If we make a mistake in our little practice of 2 million people, large swaths of the world will be hurt."

Two million is the number of HIV sufferers throughout the developing world that Mr. Bush has vowed to provide with life-saving prescriptions. Generic combination drugs could help make that goal attainable because a single daily pill is a more realistic regimen for impoverished, illiterate patients who rarely stick to the complex drug "cocktails" that require popping up to 20 pills a day.

Despite the advantages, however, the Bush administration insists generic combinations are not the panacea some would claim. For one thing, federal health officials aren't sure the drugs certified by the WHO are true generics -- drugs that are chemically identical to the original brands. The FDA wants to conduct its own tests before the U.S. government starts shelling out billions of dollars for potentially defective pills.

While the WHO carries out some regulatory functions, such as inspecting drug manufacturers on site, it is not primarily a regulatory body like the FDA, and its processes are not as transparent, according to Mary Pendergast, a former FDA official. The U.S. agency, for instance, posts on its website inspection results and extensive analyses of why a drug was approved. The WHO does not, so it's not clear whether the group is applying the same standards across the board.

And even with the best intentions, Ms. Pendergast sees a tension between recommending a drug and regulating it. "Structurally, I don't think WHO is the proper place to do quality assessment," she said. "For one thing, it's a member organization, so they have to please members" -- many of whom are clamoring for the very drug under evaluation.

U.S. stubbornness over quality received some vindication in late May, when the WHO yanked from its list two AIDS drugs it had previously recommended. WHO officials admitted that the drugs, often used in poor countries, were not chemically identical to their branded counterparts. "This admirable public acknowledgment cannot but raise questions on the acceptability of this process as a whole," said Bernard Van de Wal, an associate professor of medicine at Stellenbosch University in South Africa.

Besides initial quality, administration officials also worry about the long-term potential for increased bodily resistance to combination drugs. In U.S. treatment programs, for instance, about half the patients are already showing resistance to one or more of the drugs in their cocktail, and 10 percent are resistant to all three classes of drugs available. If those sorts of figures took hold in Africa, where some 28 million have the AIDS virus, that would render current treatments ineffective within 10 years.

The generic drug of choice among AIDS activists boosts the potential for such resistance levels, according to critics. Manufactured in India under the names Triomune and Triviro, the drug is a combination of three AIDS medications that are patented separately, but not in combination, by different Western drug makers. Triomune performed well in a study conducted by Doctors Without Borders, and comes with an attractive price tag: Its Indian manufacturer reportedly promised the Clinton Foundation they could provide a year's worth for just $140 -- half the cost of other combination drugs.

But research has shown that taken separately, the body absorbs and expels the three drugs in Triomune/Triviro at different rates. One of the three, Nevirapine, stops working after one to seven days, while the other two wear off after a few hours. Without the ability to dose separately, a patient would end up on Nevirapine only instead of all three drugs necessary. And with only one drug to fight the disease in those gap hours before the next dose, the AIDS virus can more easily mutate and become resistant to Nevirapine.

That would be a disaster in developing countries, where patients can ill afford even the cheapest generics, much less the far more expensive "second-line" drugs given to patients who've developed resistance to their initial prescription.

With the U.S. government taking a go-slow approach, the WHO is determined to press ahead on its own with medications for 3 million patients by next year -- a noble but risky goal, some experts say.

"Unfortunately, the truth today is that no single way of using anti-retroviral treatment in Africa has been validated to be the best approach in all the different parts of Africa, in different subpopulations, clinical settings and against different viral strains," says Dr. Robert Redfield, co-founder of the Institute of Human Virology in Baltimore. "This is why rather than try to treat 3 million people by 2005 by a single approach, I would rather encourage us to treat 10,000 people, 300 different ways and learn what works best."

Slowly but surely, some governments seem to be learning that caving in to public pressure is certainly not what works best. On July 13, South African officials announced the public-health service would no longer distribute Nevirapine as a stand-alone drug. (It will still be used as part of a drug cocktail.) The reason: A new study shows pregnant women who take Nevirapine develop increased resistance to the drug in subsequent pregnancies.

The country's most powerful AIDS organization immediately criticized the ban. "We think that it would be wrong of the government to simply withdraw Nevirapine," said Mark Heywood, a spokesman for the Treatment Action Campaign. "What the government needs to do is to introduce, as soon as possible, access to double drug regimens or triple drug regimens for pregnant women."

But the government is unlikely to be moved by TAC's cries. It was activist groups like TAC, after all, that went to court in 2002 to force the immediate distribution of Nevirapine despite the reservations of medical experts. Two years later the experts are vindicated and the activists discredited.

No word whether the protesters in Bangkok got that memo, either.