Newsday - June 24, 2001
Laurie Garrett, Staff Writer

The subject is AIDS.

It is the first time in the history of the United Nations that the General Assembly has convened to discuss a matter of health. Starting tomorrow morning, UN attention will focus for a week on a microbe, its devastating impact on humanity, and schemes for slowing its seemingly relentless spread.

"It is finally possible to devise a platform for action that incorporates the insights and lessons garnered over the past two decades," states a position paper released last week by Secretary- General Kofi Annan and the United Nations AIDS Programme. "At its center stands the conviction that tackling the epidemic is an indisputable, global priority, and that an expanded, extraordinary response is not simply necessary, but feasible."

Last week, as the meeting neared, donors announced support for the Global Fund to fight AIDS. On Tuesday, the Bill and Melinda Gates Foundation committed $100 million. Congress and the White House already have donated $519 million for fiscal year 2002. About $300 million more has been committed so far by European nations. On Wednesday, the Coca-Cola Co. announced it will use its vast bottling and distribution network in Africa to disseminate via trucks the AIDS prevention messages designed by the UNAIDS Programme. And Richard C. Holbrooke, who served as U.S. ambassador to the UN for the Clinton administration, announced that he will now lead the Global Business Council on HIV. His mandate is to forge further agreements from multinational corporations for funds or use of their infrastructure to help prevent HIV.

In a news conference Thursday, UNAIDS executive director Dr. Peter Piot praised such generosity, but warned emphatically that the fund will have to reach $9.2 billion in annual donations by 2005. Otherwise, Piot insisted, efforts to control HIV could be inconsequential. When the G-8 leaders meet in Genoa, Italy, next month, it is expected that donations to the Global Fund will increase, perhaps to as much as half of Piot's requested sum. That will occur, insiders say, if the UN resolutions reached this week in New York are palatable to the leaders of the eight most powerful nations on Earth.

With money less of an obstacle, the UN special session will focus on strategies for controlling AIDS-how to use those funds.

Though backroom negotiations have been underway for several weeks, and much of the UN agenda will be pro forma, hotly contentious issues remain. A Declaration of Commitment already has been drafted, and UNAIDS hopes that all 198 countries in the UN will agree to it before the special session ends at 10 p.m. Wednesday. UN officials have been at pains to orchestrate a gathering with minimal potential for conflict.

But there is still loud disagreement about priorities and the specifics of how one responds to the spread of a sexual disease. UNAIDS envisions a plan of action that leaves the cultural flavor of the sexual discussion up to each individual society, so that Swedes might allow televised explicit safe sex programs, while Saudi Arabians might prefer to inform students of the dangers of HIV in vaguer terms. Such things need not be spelled out in an internationally uniform manner, UNAIDS insists.

So the most heated discussions this week will focus on the arenas that require the most global cooperation and uniformity of action. At the top of that list is treatment.

For several weeks, global health leaders and activists have argued over where to place stronger emphasis: on treatment or on prevention. In the United States, the decision has been made: prevention efforts garner millions in government and private contributions annually, but treatment expenditures long ago eclipsed an annual $10 billion.

But Africa, South Asia, Latin America, Russia and Eastern Europe haven't the luxury of contemplating such staggering spending. So a global triage must be painfully executed.

In a large position paper released in advance of the UN gathering, UNAIDS and the secretary-general called for these priorities:

Increase Global Fund donations each year until 2005, then maintain a level of $9.2 billion a year.

Encourage all nations, no matter how poor, to spend heavily on AIDS control from their own domestic budgets. About 20 percent of the cost of waging war on global AIDS should be borne by poor, ravaged countries themselves. The higher a country's GNP, the greater the percentage of its AIDS program should be funded with domestic resources.

Of the donated $9.2 billion, allocate $4.8 billion for prevention and $4.4 billion for treatment and care of HIV patients and their families. Spend more heavily on treatment in AIDS-ravaged Africa; more heavily on prevention in Asia and the former Soviet nations, where the epidemic is still expanding.

Spend 26 percent of the treatment total, or $1.13 billion, for purchase and distribution of anti-HIV drugs in poor countries.

That distribution of dollars and emphasis will be the key target of debate this week. Many activists and national leaders feel the commitment to direct treatment of HIV infection is too small.

"There's one line of thinking that goes, 'Prevention is always the better buy, and care is too costly,'" Dr. Mary Bassett said in an interview. "My own feeling is, if you don't have a credible care system your prevention efforts are in trouble. And that's why I'm interested in investing in care."

Since Bassett, a native New Yorker, moved to Harare, Zimbabwe, more than 15 years ago, she has watched AIDS deaths soar in that southern African nation, "at a straight 45-degree angle," she said.

Now Bassett will head the Rockefeller Foundation's efforts to confront AIDS, malaria and tuberculosis in Africa.

"In Harare, the only signs of AIDS are death. Piles of coffins. Obituary pages full of faces. And it undermines the entire AIDS control effort," Bassett continued. "It completely feeds the fatalistic approach to the epidemic. And since death is so shrouded in denial, it feeds the overall national denial response."

For well over a decade, Bassett has collaborated in Zimbabwe with Stanford's Dr. David Katzenstein, conducting AIDS research. Like Bassett, Katzenstein has concluded that providing treatment will improve overall prevention efforts.

Katzenstein acknowledges that the tremendous poverty in Africa means that full-fledged American-style HIV clinical management will never be possible. But he sees no reason why clinics sprinkled across the continent couldn't offer Africans HIV testing and a combination of treatment for opportunistic infections-tuberculosis, worms, parasites-and basic antiretroviral therapy using three or four anti- HIV drugs. Katzenstein insists that without such a broadly available clinical approach in Africa all prevention efforts are doomed.

"The real terrible thing is the AIDS stigma-which is our gift to Africa," Katzenstein said during a rare visit to New York. "Because when we said, 'This HIV is terrible, it must be confidential,' we stripped away the primary cultural support-the extended family. So the consequence of having a positive HIV test in Africa is you're told you can no longer have sex, you can no longer have children, it's like a pox on you in Shakespearean times."

Offering treatment, Bassett and Katzenstein argue, means providing hope. And hope can restore that traditional family support network, destigmatize HIV and bring into the health system the 20 million to 25 million Africans who are now unaware that they carry the virus. Once in the system, the two doctors insist, the infected Africans will be willing to listen to information about condoms, safe sex and personal responsibility. But if the system has nothing to offer, the infected will never even get tested, much less sit down for a lecture on safe sex.

At this spring's Organization for African Unity summit in Abuja, Nigeria, experts concluded that only 11 percent of the estimated 25 million HIV-positive Africans have been tested.

"If you only know that 11 percent are positive you can't do prevention," Dr. Barry Bloom, dean of the Harvard School of Public Health, said in an interview. "Why do you only have that 11 percent? Because the only thing you get out of being tested is a lifetime of stigma."

To put it bluntly, says AIDS researcher Dr. David Cooper of the University of New South Wales in Sydney, Australia, "Treatment is prevention."

Some treatment advocates go a step further, insisting that as antiretroviral drugs lower the numbers of HIVs swarming in an individual's bloodstream, they also render the person less contagious.

But if, indeed, Highly Active Antiretroviral Therapy, or HAART, renders individuals less contagious to their sex partners, there is still little reason to believe treatment alone will slow down the overall epidemic, argues Dr. James Curran, dean of the Rollins School of Public Health at Emory University in Atlanta.

"The discussion about decreasing the viral load and thereby having an impact on transmission, when you're treating a few thousand people, is really out of place. It's out of place even if you're treating a million," Curran argues, because the epidemic is now so massive. Unless a third or half of all HIV-positive individuals in Africa received successful HAART therapy, the impact on the overall epidemic would be negligible.

Further, studies show HIV can be present elsewhere in the body- hiding in the lymph system, genitals and gastrointestinal tract, for example-despite being undetectable in the bloodstream after HAART therapy.

To whatever degree HAART may dampen transmission of HIV, the impact is countered by emergence of drug resistant strains of the virus.

And more and more people in the United States, Canada and Europe are getting infected with drug resistant forms of HIV. Earlier this month, researchers from the University of California and San Diego reported that surveys of those newly infected with HIV in the first months of 2001 show that 29 percent had viruses that could resist at least one of the HAART drugs. [CORRECTION: In a story Sunday on a UN conference on AIDS, the headquarters of Virologic, a company that makes resistance screening tests, was incorrectly reported. The company's headquarters are in south San Francisco. Pg. A02 ALL 6/26/ 01] Virologic, a Scottsdale, Ariz., company that makes resistance screening tests, reported two weeks ago that multidrug resistance- against two or more HAART drugs-among people newly infected in 2001 hit 6 percent-up from about zero five years ago.

The emergence of drug resistant strains of HIV is usually associated with a decline in patients' health, and 75 percent of all AIDS deaths in the United States are attributed to drug resistant HIV.

In the wealthy world, therefore, HAART treatment is a complicated matter. Patients rarely stay on a given drug combination for more than 18 months before either resistance or toxic side effects emerge. Tests are done constantly, looking for viruses, measuring immune responses, monitoring telltale signs of toxic side effects and trying to spot opportunistic infections. At the first sign of trouble, doctors usually switch to another HAART drug combination, and then another, and then another.

Nevertheless, argues Dr. Paul Volberding, director of the Veterans Administration Hospital System of Northern California, the impact of HAART "is amazing! A patient recently sent me some old videos...it blows me away to see the emaciated 'old' form of AIDS! It's a different disease today."

Volberding favors transplanting the U.S. experience with HAART to Africa on a large scale, right away. But Dr. Michael Saag, who sees nearly every one of his state's HIV cases in his University of Alabama Clinic, charges that, "the treatment community has bought- literally and figuratively-the concept that HAART saves lives...Yet we really don't know the precise point at which the benefits of HAART genuinely kick in vs. the point at which it is simply used to make the provider feel better, that they are doing something."

Earlier this year the AIDS clinical leadership in this country-in the form of elite advisory panels and the National Institutes of Health-turned treatment recommendations topsy-turvy. Instead of treating all HIV patients as early as possible in the course of their infections, the leaders said, it's best to wait until patients are roughly midway through their infection. Why? Because early treatment is more likely to lead to drug resistance and toxicity.

The list of side effects associated with HAART is long-and growing. The drugs disrupt a number of crucial metabolic functions, resulting in everything from kidney failure to loss of thigh bone tissue. Patients have had heart attacks, strokes, paralysis, nerve damage, liver failure, pancreatic inflammation, non-stop nausea, and the list goes on.

"People are suffering from severe life-threatening complications of drugs. And a lot of them get to the point where they simply can't use them anymore," Martin Delaney, director of the San Francisco- based Project Inform said on ABC Nightline recently. "So as we talk about bringing therapy to Africa...I have this pang in my heart of, are we doing the right thing with these drugs? Or are we unleashing another kind of epidemic over there of drug side-effects?"

The question may boil down to just how much life benefit can HAART provide, compared to the risk of promoting widespread drug resistance and toxic side effects. In the United States, AIDS-associated death tolls have plummeted since introduction of HAART in 1996, according to the Centers for Disease Control and Prevention. The CDC recently reported that the odds of an AIDS patient surviving for two years after diagnosis jumped from 67 percent in the pre-HAART era of 1993 to 90 percent in 1997, when most AIDS patients in America were on the drugs. But beyond that, the survival benefits of HAART are unclear, and estimates of the amount of added life average American patients gain range from as little as 18 months to more than five years. In its calculus, UNAIDS assumes that HAART will lengthen African lives on average by five years.

Most American patients, however, gain only a modicum of life unless they are in the hands of an experienced doctor and have financial opportunity to obtain a wide range of treatments and tests. The CDC and UNAIDS have provided American-style care in Ivory Coast, West Africa, since 1998. The patient dropout rate has been so high that what was originally envisioned as a test of HAART on thousands of patients now involves less than 600. And laboratory test costs, alone, for those patients have topped $600,000, according to the CDC's Dr. Harold Jaffe.

"Well, we can't do that! That's clearly not sustainable," Jaffe said.

Nobody believes that such a complex, costly approach can be executed in Africa, Asia or the former Soviet nations.

The model for use of HAART in poor countries is Brazil, where, at government expense, all HIV-positive citizens can receive the drugs. It isn't perfect. But it may be good enough, supporters say. The Ministry of Health estimates that more than half a million Brazilians were infected last year, and of that number 160,000 had been tested and 100,000 were on HAART.

The Brazilian program is run by Dr. Paulo Teixeira, who said in a recent interview that infection rates in most Brazilian population groups have fallen by about half since 1996, mainly because the government aggressively distributes condoms. Last year 650 million condoms were distributed free in Brazil.

All blood tests are done in a couple of dozen centralized laboratories, Teixeira said.

"We did not control AIDS," Teixeira said. "But we have improved it. And we have shown we can make a difference."

Can that difference translate to far poorer nations? Taking treatment to the masses of the world also will mean confronting corruption. For example, in April, it was discovered that scientists working in Pakistan's national AIDS program stole $60,000 worth of HIV testing equipment, selling it on the black market. In May, the Russian government refused to accept $150 million worth of donated anti-tuberculosis drugs, most of which would have gone to AIDS patients, on the grounds that it would undermine the local pharmaceutical industry. In the June 16 issue of the British medical journal Lancet, a team of British and Nigerian scientists published evidence that 48 percent of all drugs purchased in Nigerian pharmacies were counterfeit or improperly dosed. And in Zambia, AIDS activists are up in arms over discovery that most of the revenue from an international AIDS meeting hosted by the Chiluba government last year ended up in the hands of a few politicians who allegedly used the funds to buy themselves cars and houses.

Dr. Subash Hira is one of a handful of doctors in the world who has been caring for people with AIDS since before the disease had a name. During the first decade and a half of the epidemic, Hira oversaw treatment of all sexually transmitted diseases in Zambia. For the last several years, he's been working in his native land, India, caring for HIV patients in Bombay.

He finds the recent debates about treatment vs. prevention priorities disturbing because they make, "we who have lived and worked in Africa and Asia feel that there is no place for science. We continue to hear that massively increased levels of resources on a sustained basis are required to respond to the epidemic. One wonders what these nations are going to do with additional resources if the existent resources are not put to proper use."

Hira argues that the "mainstay should be prevention," that is integrated into a long chain of activities, culminating in treatment of AIDS patients and support for their orphaned children.

"I doubt if many countries in Africa and Asia will be able to demonstrate the complete chain," Hira said, especially outside the largest cities. For rural Asians and Africans, who make up 60 percent of the continents' populations, "one generation simply follows another," Hira concluded. "How are we going to interest these folks to listen to AIDS prevention, let alone practice safe sex?"

CORRECTION: In a story Sunday on a UN conference on AIDS, the headquarters of Virologic, a company that makes resistance screening tests, was incorrectly reported. The company's headquarters are in south San Francisco. Pg. A02 ALL 6/26/01
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