March 2002


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Written by
Kris B. Mamula

Photograph by Richard Kelly

One man has lived with AIDS for more than 20 years. His nearly two-decade-long participation in the Pitt Men’s Study has provided researchers with new insights into the virus. The research reveals how those diagnosed with AIDS can better maintain their health and improve their quality of life.

Walking Miracle

The fading afternoon sun outlines a man dressed in white as he works on a miracle.

He starts by telling the story of six guys who turn up at a wedding reception uninvited. No one much cares, except the mother of one of the men. She’s there helping. To her son she whispers: “There’s no more wine.”

Absorbed in the story is a tall man, all kneecaps and elbows, who sits in the front row of the Community of Reconciliation chapel, roughly a block from the Cathedral of Learning. He chews bite-size pieces of peppermint and toffee candy that he slips one at a time from his khaki pants pocket. On the floor by his chair sits a plastic bottle of Dasani water. He tilts back his head, a nest of styled gray curls, and gulps. It’s the medication, he says. It makes his mouth dry. He leans over so his voice won’t disturb the service. Dangling from a silver chain under his short-sleeve shirt is a medal of St. Francis of Assisi, a 12th Century playboy whose conversion began with his embrace of a leper.

The man in white closes in on the miracle. The mother orders the kitchen help to do whatever her son tells them. The son wants stone jars filled with water. Poof, it’s wine.

The man in the front row has heard about Jesus’ first miracle hundreds of times throughout his 62 years. When the gospel ends, he gets to his feet slowly, as though his tan loafers are filled with marbles. He shuffles to the altar and holds hands with members of the congregation. “Lord, I am not worthy to receive you,” they pray, “but only say the word and I shall be healed.”

The man’s name is August Pusateri. Not even his family calls him by that. He has been known as Buzz for as long as anyone can remember. Pusateri is a retired pharmacist. He is also the son of a Pittsburgh produce wholesaler and a mother who could hold her own unloading trucks for the family business. He has a drawn face, and Groucho Marx eyebrows. Worry makes his eyebrows knit into a black point between his eyes. He is easily winded, his gentle laugh little more than a whisper.

Pusateri knows miracles. He has acquired immunodeficiency syndrome. Against all odds, he has lived more than 20 years with the disease better known as AIDS, since before anyone even knew what to call it.

“[Pusateri] is our new paradigm for the face of the epidemic in America.”

—Charles R. Rinaldo Jr., principal investigator of the Pitt Men's Study at the Graduate School of Public Health.

AIDS is an incurable disease caused by the human immunodeficiency virus (HIV). The Centers for Disease Control and Prevention (CDC) estimates that HIV infected some 40,000 Americans last year and about one-half of these people probably don’t know they are infected. What’s more, AIDS cases nationwide have been rising for the past two or three years, says Helene Gayle, director of the National Center for HIV, STD, and TB Prevention at the CDC. Worldwide, Pusateri is among an estimated 36 million men, women and children who are infected with HIV, according to the United Nations. That’s more than the population of Canada. A few days before the Mass in Oakland an international public health group warned that AIDS threatens world security. John W. Mellors—professor of medicine at the University’s School of Medicine and chief of the infectious diseases division—is not optimistic about the future. “There’s going to be a huge human toll exacted by HIV,” Mellors says. “When I look in the crystal ball, I see an expanded global epidemic.”

Meanwhile, Pusateri faces the miracle of middle age. This after surviving two infections, which killed many others with AIDS. Dying just wasn’t an option, he says, shrugging. New drugs helped reverse the odds. “He is our paradigm for the new face of the epidemic in America,” says Professor of Pathology Charles R. Rinaldo Jr., founder and principal investigator of the Pitt Men’s Study at the Graduate School of Public Health (GSPH); and chairman of the school’s department of infectious diseases and microbiology.

But the marvel of longevity has a dark side. As recruitment coordinator for the Pitt Men’s Study, Anthony Silvestre has tracked the ravages of AIDS since it was first reported in 1981. He is alarmed by a steep decline in the number of men being tested for AIDS since 1996. While testing is down, the number of AIDS cases is up nationwide. Some youth even carelessly wonder whether safe sex is worth the fuss. “The kids think the pills will work,” Silvestre says glumly.

Problem is they’re only half-right.

A virus has only one goal and it has not changed in eons: Reproduce. Like all viruses, HIV reproduces by barging into a healthy cell and snatching its genes, the recipe the cell uses to duplicate. The infected cell then begins churning out copies of the virus instead of healthy cells. A virus’ ability to adapt is quite something. The ability of the AIDS virus to adapt is frightening.

The AIDS virus’ adaptability begins with a reproduction process that Pitt AIDS researcher and professor of medicine Michael A. Parniak calls sloppy. Here’s why. AIDS turns a healthy cell into a bomb factory gone berserk. Instead of identical duplicates, the factory spews imperfect copies of itself—hand grenades, land mines, SCUD missiles. Some differ by only one or two tiny amino acids. In a new infection, a drop of blood teems with roughly one million bits of virus, Mellors says. But only one percent of these bombs can spread disease. Cranking full blast 24-7, the HIV assembly line spills billions of imperfect viral duplicates into the blood. The sheer number and subtlety of differences guarantee that some copies will survive. Some will be killers. But that’s not the worst of it.

HIV attacks immune system cells. Its main target is CD4 cells. Think of these cells as army generals. They trap invaders, such as the virus that causes the common cold, then act as the eyes for the immune system’s infantrymen, which are called CD8 cells. When HIV cripples the early warning immune system cells, what remains is a fort defended by soldiers with their eyes gouged out. Even that’s not the worst.

“There's going to be a huge human toll exacted by HIV. When I look in the crystal ball, I see an expanded global epidemic.”

John W. Mellors, chief of the Division of Infectious Diseases and director of the HIV-AIDS program at Pitt.

HIV is a fussy eater. It craves CD4 cells, which are switched on, ones that already recognize the invader. HIV very quickly adapts to the idiosyncrasies of the individual’s immune system, Mellors says. That means the virus molds itself to its host in ways researchers only dream about doing one day with medications. A person may only feel a little crummy when first infected. Deep inside, the body’s defense scaffolding is quietly collapsing.

HIV is the most studied virus on the planet. In fact, more is known about the virus today than was known about polio when Jonas Salk discovered the vaccine at Pitt in 1952. Without a vaccine, AIDS therapy aims simply to kill the virus.

Pusateri doesn’t so much make his semi-annual exam as he whirls, breathless, into the Pitt Men’s Study office. He wears a short-sleeve, purple pullover with matching tee shirt, navy shorts, and white sneakers. Outside, it’s 75 degrees, boiling its way to 90. The waiting room calendar has a message: The Greatest Prayer is Patience. Pusateri sighs deeply. With manicured fingers, he jams black-frame glasses up the bridge of his nose. His day is full. It’s getting hot. He’s running seven minutes late.

“How ya feeling?” research associate Scott McCauley asks, handing Pusateri a questionnaire. Pusateri answers in a nasal monotone with a rundown of his plans today. First stop is Sam’s Club. There, he will load his 1991 Plymouth Sundance with groceries for a dinner that he’s helping prepare for people with AIDS. Two things he doesn’t mention: In a few weeks, the Lambda Foundation will launch the Buzz Pusateri Alpha to Omega AIDS Fund to benefit AIDS research. And next month, Pusateri will host his annual Mass in the backyard of his home in the city’s Friendship neighborhood. He sighs again, like the sound of corn stalks roused by an October wind.

Breezing into the exam room, Pusateri sheds his shirts and offers his forearm for a blood draw. His movements have a practiced quality, almost mechanical. He lies back on an exam table, and technician Bill Buchanan ties off his arm with a rubber strap. Meanwhile, McCauley begins the drill.

T-cell count less than 200?
Yes, since January.
Elevated cholesterol?
Yes, also since January.
Burning/aching feet?
Three on a scale of one-to-10.
Mother was diabetic. Also stroke and heart problems. No, no hepatitis. Alcohol—rarely. Four, maybe five times yearly. One drink.

With a plastic tape, physician-assistant Bridget K. Calhoun measures the circumference of Pusateri’s arms, legs, and belly. Only now, with AIDS patients living longer, have side effects of the latest antiretroviral drugs begun to emerge. In the mid-1990s, these drugs moved AIDS care from the intensive care unit to the doctor’s office, almost overnight. But there are side effects. In recent years, Pusateri’s face has become drawn, and he has a new potbelly. This occurrence has a medical term: fat redistribution. Numbness in his feet is another side effect. Not all of the side effects are known. Pusateri stands. That sigh. His eyes roll toward the ceiling as his height is recorded. Then temperature: 98.1. His feet are cold. At 11:12, the exam ends. He dresses quickly, as though trying to outrun a clock.

Pusateri’s evaluation comes 20 years and eight days after the CDC reported that five Los Angeles homosexual men died from a rare form of pneumonia. Within months of the report, Rinaldo formed the Pitt Men’s Study. No funding, no government grants. Just a group of Pitt researchers worried about a mysterious disease that was turning up in the gay community. The group’s first task in 1982 was interviewing and collecting blood samples from people believed to be at risk of developing a strange new disease. A year later, the National Institute of Allergy and Infectious Diseases, a federal agency, organized the Multicenter AIDS Cohort Study (MACS) to learn more about the virus. MACS is the biggest study of gay men in the history of science.

Federal research funding then became available, and GSPH became one of only four MACS sites nationwide. Pusateri was among 1,000 gay men in the Pittsburgh area who volunteered in 1984, the first year. “It was a way I thought I could help people down the line,” he says. An aggressive educational campaign in Pittsburgh’s gay bars and clubs was part of the recruitment effort. Volunteers were offered free screening for colorectal cancers, diabetes, and other diseases. Hospice was the only resort for those with AIDS then. But researchers believed that a bank of blood samples from people with the disease, or who were at high risk of getting the disease, might contain clues. Their hunch was right.

Blood samples and other data collected by the MACS soon began yielding startling insights. Let’s start in the 1980s, when the spread of HIV was poorly understood.

Pitt researchers, led by Lawrence A. Kingsley, discovered in 1986 that receptive anal intercourse was the most likely route of infection. Safe-sex educational campaigns followed. The results were striking. Before the study, some 20 percent of MACS’ volunteers were getting the disease each year after having first tested negative. After the study, the rate of infection among study participants plunged to 1 percent annually. It has remained in the low single digits since then.

More recently, research led by Mellors—director of the University of Pittsburgh Medical Center’s HIV/AIDS Program—found the amount of virus in the blood is the most reliable marker of disease progression. Previously, doctors used T-cell count as a barometer for treatment decisions. Viral load today is the standard for identifying HIV’s progression.

The future of AIDS research at Pitt is promising. With support from the National Institutes of Health,* Rinaldo is looking at ways of turbo-charging a certain kind of dendritic cell. Dendritic cells are like army scouts, potent weapons in the body’s early-warning defense system. HIV hobbles the immune system’s generals and infantrymen, even after the blood has been cleaned of the virus. For that reason, killing the virus is not enough. A way to boost the body’s defenses is needed. Rinaldo says dendritic cells might be the key.

The Pitt Men’s Study, part of the largest project of its kind in the world, is reaching out for more volunteers. Here’s why. Only 12.4 percent of men in the United States are African-American, according to the US Census Bureau. But more research is needed to find out why a full 50 percent of newly infected men are black. By September, the Pitt Men’s Study goal is to double to 800 the number of gay or bisexual African-American volunteers.

Despite all the promise, the hoopla, the breakthroughs, the epidemic’s biggest challenge may just now be unfolding.

Before 1993, people with AIDS were given the drug AZT. Nothing else worked. AZT didn’t work for long, either. The virus simply mutated. Hand grenades with two detonators instead of one, maybe. The drug became useless. Combined drug therapy, which was the standard of care from 1993 to 1995, had much the same result. Real progress wasn’t achieved until after 1995 when a potent family of antiretroviral drugs became available. They really worked. Although the virus continues to smolder in the brain, prostate, and other organs, the new drug cocktails virtually eradicate HIV from the blood. But there’s a hitch.

HIV easily outsmarts assault by one drug at a time. That was AZT’s painful lesson, a lesson learned only after many people with AIDS developed drug resistance. Drugs given in combination make the difference. But that’s not how drugs are made by today’s pharmaceutical industry. New AIDS drugs are marketed one at a time, and on a timetable known only to each manufacturer. The drip, drip, drip of new drugs into AIDS clinics around the world is giving the virus a running start, Mellors says. For example, University of California researchers are forecasting that 42 percent of HIV infections in San Francisco will be resistant to current AIDS drugs by 2005. Robert M. Grant, a virologist at the University of California’s Gladstone Institute of Virology and Immunology,* sees the problem from a different view. Drugs are failing in up to half of AIDS patients during their first year of treatment. Resistance is the culprit, he says.

What’s needed is the impossible. Competing drug makers must cooperate, Mellors says. Coordinated drug release and testing are vital, especially since some researchers believe it may be 10 years before an AIDS vaccination program is up and running. “We need to work together if we are going to conquer this disease.” Mellors understands well the difficulty of cooperation. “It would be like Coke and Pepsi teaming up to make a soft drink.”

Gregory Reaves, spokesman for pharmaceutical giant Merck and Company, Inc.,* sees the problems posed by drug resistance in a different way. The ultimate solution, he says, is a vaccine. Pitt is among 61 places worldwide where Merck’s AIDS vaccine is being tested. “Vaccine therapy is the way most experts see to combat the disease,” Reaves says. A vaccine is the company’s primary focus now.

On a bedroom dresser in Pusateri’s apartment is a crystal figurine. It’s Mary, mother of Jesus, whose faith made the water-into-wine miracle possible. Pusateri is in the living room. He relaxes in a stuffed chair upholstered in a lively stripe. “I’m able to live a rather normal life,” he says, weary. “But my existence runs around these pills.” Thirty-four of them every day, at a cost of $5,000 a month. “I don’t know how long this cocktail will keep me going.” Still, he no longer thinks this may be his last Easter, his last Christmas. You don’t plan, then all of a sudden you begin looking ahead a year. “I just pray like this,” he says, opening his hands. “And I say, ‘God, you’ve gotten me this far. Now it’s up to you to get me where I’m supposed to be.’”

Good news from Pusateri’s check-up: His T-cell count, a measure of his body’s ability to fight disease, is up to 104. That’s a high for the year. In 1995, it was three. Normal is 1,000.

And how about that—tomorrow is the first day of summer. Time to take down the spring wreath from the outside door, he says, the one with the blue bird and silk dogwood flowers. In the pantry, behind the door, he carefully pulls another wreath from a white plastic bag. Here’s the summer wreath. He starts to grapple with a tangle of grapevines and leaves, twisting this one and that one into place, before it’s even out of the bag.

—Kris B. Mamula is senior editor of this magazine.

An alarming statistic

Fully 50 percent of new AIDS cases are African-Americans, even though African-Americans make up less than 13 percent of the American population.

The Pitt Men’s Study, which has yielded a number of breakthroughs during the past 20 years, is responding to this disparity by aggressively recruiting African-Americans for its long-running study. For people with the disease, UPMC offers the latest therapies. Still, that’s not enough, says Stephen B. Thomas, director of Pitt’s Center for Minority Health, and the Philip Hallen Professor of Community Health and Social Justice, a joint appointment in GSPH and the School of Social Work.

Prevention through improved community education and a better understanding of cultural differences is needed, Thomas says. The failure to reach minority populations is both a tragedy and an opportunity, he adds.

AIDS isn’t the only disproportionate health problem in the African-American community. For example, the death rate for all cancers is 30 percent higher for African-Americans than whites, according to the National Institutes of Health (NIH). What’s more, minority and poor communities lag behind the overall US population on virtually every health status indicator.

New strategies are needed to reach these groups, says Thomas. “We’re not translating what we know and progress is limited because of that.”

The Center for Minority Health has embarked on a number of educational efforts, including improving the cultural sensitivity of researchers, physicians, nurses, and other healthcare workers. Supported by an NIH grant, Thomas is also spearheading a study on how to increase minority participation in clinical trials.

—Jennifer Meccariello

*—denotes an external link. Links to external websites are offered for informational purposes only and the information there is not guaranteed or endorsed by the University of Pittsburgh or its affiliates.

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