Newsday - May 29, 2001
Laurie Garrett, Staff Writer

"What is the future of the AIDS pandemic?"

Krim has devoted the past two decades of her life to combating HIV. It's a battle without many victories.

"That is too terrible to consider," she says.

The Swiss-born founder of the American Foundation for AIDS Research-a leading HIV charity in the world-uses the words "disaster," "catastrophe" and "true horror" to conjure her view of humanity's largest epidemic -one that will shortly surpass the Black Death of the 14th century for numbers of humans infected and killed.

Twenty years ago, Krim, now in her 60s, was one of a handful of physicians and scientists in the United States who took note of odd clinical events transpiring among homosexual men. On June 5, 1981, the first official notification of the development was published in the Centers for Disease Control and Prevention's publication, The Morbidity and Mortality Weekly Report. That historic paper, authored by Michael Gottlieb, a physician at the University of California at Los Angeles, took note of a cluster of cases of Pneumocystis carinii pneumonia found in otherwise healthy, young, gay men. Because that form of parasitic pneumonia was usually controlled effectively by the human immune system, only cancer or transplant patients typically were susceptible to the microbes' devastation of undefended lungs- and eventual death.

A month later, the CDC published word of another bizarre ailment, also being seen in gay men: Kaposi's sarcoma. A rare form of skin cancer, KS, too, was previously seen only in highly immune-deficient individuals.

Today Krim lives in a skyscraper apartment that-appropriately, she thinks-overlooks United Nations headquarters. The AIDS battlefield that 20 years ago seemed isolated to pockets of America's gay community has wrought worldwide devastation.

It has infected 60 million people since 1981. Twenty-three million of them have died.

And that's only the toll of history. What looms ahead-and forecasts range from the conservative to the dire-leaves Krim and others with little optimism.

The range of estimates looking ahead 20 years runs from a low of 5 million deaths to more than 12 million each year. Some put the annual tolls at 2 to 3 percent of a country's entire population.

"I was there at the beginning of the epidemic. But I'm sure I won't be around for the end," Dr. David Ho says, shaking his head. Ho, 49, directs the Aaron Diamond AIDS Research Center, with an office just a few blocks away from Krim's aerie. Like Krim, two decades ago Ho took note that "something was clearly wrong" among the gay patients he treated as the then-chief medical resident of Cedars- Sinai Medical Center in Los Angeles.

It was Ho's patient samples that were sent to Gottlieb and described in that first CDC bulletin.

"The clinicians all could see something was profoundly wrong with their cellular immune systems," Ho recalled in a recent interview. "And that's when I said, 'This is fascinating. I want to study the cause of this.'"

Little did he know it would end up occupying his lifelong career. Born in Taiwan, Ho has built research bridges between his Manhattan lab and China. He sees a grim future for that region.

"The [Chinese] government is predicting 5 to 6 million HIV cases by 2005," Ho says. "If we don't have a preventive vaccine and we don't have a preventive [vaginal] microbicide, the epidemic's size will depend on how effective the education levels have been."

He offered this scenario: "If you think 5 percent [of the population will be] HIV-positive globally, you know what the numbers will be by 2021? In 20 years? Five percent of 8 billion."

Four-hundred million people.

"Some would argue that in India and China, we won't see the African scenario play out," he says. "I agree-maybe not 25 percent [prevalence of HIV]-but 5 percent, that's enormous. That's my fear."

The African scenario: Those words are charged with apprehension and despair by the policy-makers who speak them. Infection rates in the 49 nations below the Sahara range from about 4 percent of adults to a high of 46 percent in parts of South Africa.

Last month, Dr. Marsha Coleman-Adebayo, chairman of the Washington, D.C.-based International African AIDS Network, issued an open letter to African heads-of-state: "The AIDS crisis is draining Africa of its best and brightest workers," she wrote, "farmers, school teachers and children-indeed, of its very future and existence.

"More than 5,000 people with AIDS die each day in Africa and epidemiologists expect that figure to climb to approximately 13,000 by the year 2005. Within the next 10 years, it is projected that there will be 40 million AIDS orphans in Africa."

Earlier this month, at the Geneva gathering of the World Health Assembly-the governing body of the World Health Organization- Mozambique's Minister of Health declared, "In 10 years', 15 years' time, we might have no people living in some countries! Time is going by and we are spending our time in meetings, and meetings, and meetings. And time and death is marching!"

One of today's epidemic seers is epidemiologist Andrew Moss, who has been tracking AIDS from his perch at the University of California at San Francisco since 1981. Back then he told a skeptical San Francisco community that about half of its gay population was already infected. No one wanted to believe him, for those were days before HIV blood tests could-and eventually would-prove Moss right.

Today, the avuncular, British-born Moss says this of 2021: "I actually do believe it's an apocalyptic event, the worst event in human history. We should use the 19th century and syphilis as our guide. It's a terrible thought."

He says syphilis, which proved impossible to control until the mid- 20th century invention of antibiotics, had sexually infected about 20 percent of draft-age men by World War I. "And [HIV] is definitely that bad. It's going to be everywhere, all over, I'm afraid."

No weapon comparable to antibiotics has been developed to attack AIDS. The word "cure" is rarely used by scientists in this war because HIV targets human genes and hides inside the DNA of cells. Nobody knows how to destroy viruses hidden inside DNA without damaging human genes in the process.

Undeterred by effective vaccines or treatments, AIDS prevails. And forecasting its path has proven a tricky business. It's every bit as hard to factor all the sexual, political and behavioral aspects of HIV transmission into a crystal-ball view of the AIDS epidemic as it was during the mid-19th century explosion of syphilis in Europe, Moss says. The one hallmark of HIV forecasts has been underestimation, notes epidemiologist Jim Curran, dean of the Rollins School of Public Health at Emory University in Atlanta. "Every forecast has proven way too low," he says.

Like Krim, Ho and Moss, Curran has been on the HIV frontlines since 1981, when he headed the CDC's original efforts to grapple with HIV's emergence. And Curran says that even now, "in the United States we really don't know how many people get infected each year."

Epidemic forecasters use a variety of methods for reckoning the future. Curran, for example, is hesitant to even assign specific numbers to a 20-year forecast. But he says one method needs to be dismissed: The reliance on classic acute outbreak studies that look for evidence of natural immunity in a population, prompting an epidemic to level off and then curve downward without the benefit of vaccines or cures-the "bell-shaped curve" of epidemics. "That's a lot of garbage," Curran says. Rather, he explains by phone from his Atlanta office, HIV should best be compared with the tolls of such ancient killers as gonorrhea, malaria and tuberculosis.

"You have all these millions of carriers out there," Curran says, "so you have to look at things like an achievable endemic level"- when it reaches a stable plateau, becoming a permanent feature in a population.

Curran suggests that, in the absence of a vaccine, moderate endemic levels may be the most optimistic result. Even then, it could take years to reach that plateau.

And in the absence of effective treatments, he says, "you can assume that...the numbers of new infections will equal the numbers of deaths each year, giving you a sort of natural stabilization rate."

Dr. Harold Jaffe has worked on HIV for 20 years at the CDC. He looks at the world today as an HIV patchwork: The rates of infection vary widely, from no more than 1 percent in North America and most Western European nations, to 40 percent and higher in parts of Africa. AIDS may have already reached endemic heights in some countries, while continuing to escalate in others. What constitutes an endemic prevalence varies from country to country. And the differences are mysteries.

"We still don't really understand well why infection rates seemed to stabilize at certain levels, and why they vary so much from country to country, region to region," Jaffe says.

For more than a decade, the U.S. Census Bureau has used sophisticated computer models to track this patchwork, creating reliable estimates for each nation of year-by-year growth. Its approach is fairly cautious-yet the forecasts are bleak. Today's infection rates reflect the bureau's worst-case scenario forecast made a decade ago, says Karen Stanecki, who leads the bureau's team of plague forecasters.

Like Curran and Jaffe, Stanecki thinks some level of stability has been reached in a few African urban centers, "but in the rural areas we still see the potential for sharp increases."

How far could these increases go? "It's really difficult trying to understand this," Stanecki says. "Nobody ever expected prevalences to reach 40 percent, but then we topped 46-percent infection rates in KwaZulu Natal [province of South Africa]. That was a real shock.

"And where it stops, no one knows."

Stanecki's team has prepared forecasts through 2050-though she's quick to note that the further into the future predictions go, the less reliable the reckonings are likely to be.

The predictions point up the variability between countries-due in part to the age of a given country's epidemic. For most nations, HIV is a fairly new invader, and the people haven't witnessed the staggering death tolls that have claimed populations in, for example, Africa's Lake Victoria region.

Stanecki uses Francistown, Botswana, as an illustration: It has an HIV rate among adults of 42 percent, yet the dying has only just begun-because the disease process takes roughly 10 years, and the virus only began sweeping through the nation during the early 1990s. This year, the disease is reaching its advanced stage in most of the first wave of people infected, and more than 70 percent of all deaths in the country will be due to AIDS. When deaths occur on such a scale over time, Stanecki predicts the society will undergo social upheaval. That, in turn, could lead to behavior changes that may eventually slow it down.

Stanecki says she thinks most of North America, Europe and Japan have had stabilized, endemic infection rates for several years. But India, China, Southeast Asia and the former Soviet Union are in the very beginnings of rapidly growing epidemics.

Brazil, she says, is at its peak, with about 623,000 AIDS-related deaths a year. By next year, she says, Brazil's epidemic should begin a slow descent, with deaths estimated at 53,000 per year by 2050. The net effect will be roughly 24 million fewer Brazilians by mid- century than if AIDS had not arrived.

As staggering as that seems, Brazil is something of a success story. Many observers credit the government's commitment to public education, free treatment programs, needle distributions to IV drug users and a host of preventive campaigns.

In contrast, the 49 sub-Saharan African nations will, collectively, reach their epidemic peak in 2020, when 6,427,000 people are expected to die annually. Even by 2050, in the absence of a preventive vaccine, Africa will be losing nearly 1.5 million people each year to HIV and its leading opportunistic infection, tuberculosis.

In Western Africa, Stanecki predicts, Nigeria and the Ivory Coast will be among the hardest hit. The Ivory Coast will peak in 2020 at 220,000 deaths per year, or about 1 percent of its population. By 2050, it will have 15 million fewer people than it would have had without AIDS.

Among the Census Bureau's other projections:

Africa's most populous nation, Nigeria, will peak in 2020 at 1,250,000 deaths per year. And by 2050, its population will be 73 million below its non-AIDS forecast.

South Africa, which now has some of the highest HIV rates in the world, will peak in 2010 with 940,000 deaths each year, or roughly 2 percent of the population. The following year Zimbabwe will peak at 295,000 deaths, almost 3 percent of its population. But neighboring Zambia won't peak until a decade later.

In the Americas, Haiti will have the worst future, with HIV claiming 39,000 people in that tiny island nation each year from 2017 to 2023, or about 0.5 percent of the population annually.

Southeast Asia nations will reach epidemic peaks between 2015 and 2025, with the exception of Thailand, which is estimated to have reached a peak of 66,000 deaths per year. Myanmar, formerly known as Burma, will reach a 0.1-percent annual death toll by 2015, claiming 97,000 lives. And Cambodia will peak from 2017 to 2024, with 31,000 annual deaths.

Moss is conducting epidemiology research in Cambodia and Vietnam, a region he says is plagued by a double whammy: heroin use and an enormous female sex industry. "It's hard to be optimistic" about the futures of those nations, he says.

The epidemics in Russia, Ukraine and other parts of the former Soviet Union are growing so rapidly that few agencies are prepared to issue forecasts. The Russian Ministry of Health recently released estimates saying 113,000 people are HIV-positive, "minimally." The ministry estimates 100 Russians, 70 in the Moscow area, are newly infected every day.

The country's five-year forecast, published earlier this month by the Russian Federal AIDS Center, is that by the end of 2005, every 30th inhabitant of Russia-or 5 million people-will be infected. The Ministry of Health predicts that roughly 12 percent of the Russian population will be HIV-positive by 2015.

In his address to the World Health Assembly in Geneva earlier this month, Ukraine's Minister of Health said his country's epidemic had worsened severely, with "75 percent of all HIV cases being intravenous drug users...and there is a trend towards spread in the affluent areas, where we see an increasing number of cases in women and children....The acuteness of the situation cannot be overstated."

There is one iconoclast in the community of forecasters. Jim Chin has a far less grim view of the future. During the 1980s, he did AIDS forecasting for the World Health Organization, and continued to perform that task for the Joint United Nations Programme on HIV/AIDS (UNAIDS) after it was created in the early 1990s. Today Chin lives in Berkeley, Calif., and consults with governments in Asia. And he says there never will be a major HIV explosion in Asia, nor will Africa's toll reach the horrible extremes cited by the Census Bureau.

"What you see now is what you're going to get for the next 10 to 20 years," Chin says. "It's not going to go down below 10- to 20- percent prevalence in African countries. But it's not going to get above 20 percent, either. And in Cambodia [and] India, there will continue to be stable incidences connected to sex workers. But it's not going to be much worse in Asia. It's pretty much peaked."

Chin bases his forecast on patterns of social mixing: A look at who in each society tends to interact with other groups of people in ways that can spread the virus. He says heroin users rarely mix with non-users, so HIV stays within those narcotics communities. Similarly, he says, prostitutes and the men who frequent them form a unique social network that has little overlap outside their nexus.

"Only in Africa," Chin says, "does the multi-partnering extend well beyond the sex industry, so you've got more spread." HIV, he says, thrives only where it is socially acceptable for men to have many sex partners: prostitutes and girlfriends or spouses. And he says that only Africa meets that criterion.

Moss applauds Chin for acting as a sort of "intellectual provocateur." But, Moss says, Chin has low-balled the pandemic consistently for two decades, proving correct about modest estimates in just two striking cases: the Philippines and Indonesia, neither of which has yet experienced HIV explosions.

And Moss concedes that little is known about Asian social mixing. Stanecki politely refers to Chin as "the furthest to one extreme," but says India's prevalence already tops 1 percent and Southeast Asia is, indeed, exploding with HIV.

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