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Youngest Victims

By Ann Griswold

Maureen Goodenow leads UF's efforts to understand AIDS in children

Seven is a peculiar age. At seven, kids know what’s going on, but often not why. They have their suspicions about the Easter Bunny, but haven’t quite figured out where all those chocolate eggs come from.

It’s that poignant mix of naivete and pragmatism that makes it hard for parents to deliver bad news. They worry about how much to reveal when a pet dies, or worse, a family member.

So how do you explain to a 7-year-old that he has a deadly virus before he even knows what death means? And furthermore, how do you tell his brothers, ages 8 and 9, that they’re also infected?

It may sound like an unlikely scenario, but that’s exactly what happened to Clifford and Louise Ray of Arcadia, Florida, when their three sons received blood transfusions tainted with HIV.

That was back in 1986, when few people had heard of the virus and even fewer people understood how it was — and wasn’t — transmitted. The family’s treatment as social pariahs drew national attention: They had to go to federal court to ensure the boys — Ricky, Robert and Randy — could continue going to school. After receiving several ominous threats from neighbors, their mobile home mysteriously burned to the ground. Ricky died in 1992, Robert in 2000. Randy survived and manages his AIDS with medication.

Shifting Landscape

Although public sentiment toward people with HIV/AIDS has softened over the past 20 years, the number of cases has skyrocketed: Today, more than 1 million people are infected in the U.S. alone, and more than a tenth of them are Floridians. Since the epidemic began in 1981, more than 9,000 Americans under the age of 13 have been diagnosed with full-blown AIDS. That amounts to a lot of parents breaking difficult news to their kids.

But future families might be spared that heartache if the efforts of UF researcher Maureen Goodenow and her colleagues pay off.

“One of the reasons we became involved in HIV research was the lack of treatments for the mothers or their babies,” says Goodenow, the Stephany W. Holloway University Chair for AIDS research in the UF College of Medicine. “In the late ‘80s and ‘90s, it was heartbreaking because the children with HIV infection were so ill and the physicians had so little to offer them.”

In the mid 1990s, Goodenow and her team decided to try something new. They began mapping the journey of HIV through the bodies of four children who had been infected at birth, in hopes of understanding more about the virus that causes AIDS.

Previous studies relied on cell culture or animal models to follow the virus’ mutations over time. But the UF researchers were among the first to study the progression of HIV in human patients.

“It’s not the type of study you set up to do prospectively,” Goodenow says. “We enrolled them to get blood samples over time. Death was not a desirable outcome, although it was pretty inevitable at that time.”

After following the children for more than eight years — taking blood samples at birth, throughout life and just after death — the scientists began to paint the world’s first picture of how the virus changes over time.

“Previously, the only thing known was that somehow the HIV population mutates. And as soon as that happens, patients start developing AIDS. But no one knew how or where the population evolved over time,” says Assistant Professor Marco Salemi, Goodenow’s colleague in the Department of Pathology, Immunology and Laboratory Medicine.

R5 To X4

To find out what route the virus takes after entering the body, Goodenow’s team focused on a protein called gp120 that helps HIV attach to human cells. Using a computer modeling program, they were able to sit back and watch as various mutations accumulated in the protein. Based on the position of the mutations, they were able to categorize the virus into two groups, R5 and X4.

They discovered that HIV gradually changes and matures as it winds its way through various organs in the body. Right after infection, the R5 population is present in high numbers. But just before HIV gives way to full-blown AIDS, the relatively benign R5 variants morph into a potent X4 population. It’s all downhill from there.

“Evolution of the X4 viruses is not a good prognostic indicator,” Goodenow says. “If we could understand the selective pressures that push viruses to develop like that, we might be able to set up new targets for drug development.”

That’s not a new conundrum: The origin of the X4 viruses has puzzled scientists for years. Until the UF researchers published their findings last September in the online journal PloS ONE, no one knew if the population appears spontaneously — just before the onset of AIDS — or if it had been there all along, laying low until it was ready to strike.

The researchers tackled the problem by monitoring blood samples from various organs, patiently waiting to see when and where the telltale X4 population would first appear. Their results disproved the hypothesis that X4 viruses hide out in the body all along. Rather, the scientists showed that the X4 population appears to evolve directly from the R5 variants. And it happens in the thymus, a small organ located behind the breastbone that is responsible for immune cell development.

“We found that the late-stage viruses, the X4 viruses, were localized predominantly in the thymus,” Goodenow says. “It says that the thymus is the place where these viruses develop, or at least where they’re localized and replicate.”

The researchers also discovered that HIV follows a similar path, regardless of variations in the patients’ medical histories. After hanging around for awhile in the thymus, the more potent viruses spread to the spleen, lungs and lymph nodes, where the multi-year journey comes to a fateful conclusion.

The next step, Goodenow says, will be to track the evolution of HIV in adults before and after treatment. The researchers hope their findings will pave the way for new drugs that interfere with the virus’ ability to evolve in the thymus.

“We’re starting to see what looks like a program of virus development over time. And it doesn’t matter who the person is. And it doesn’t matter what the time scale is,” Goodenow says. “It’s raising the possibility that, in fact, the evolutionary track of the virus is not totally random. There could be a real developmental program that the virus goes through.”

Road Ahead

Thanks to recent advances in drug development, an HIV/ AIDS diagnosis is no longer an automatic death sentence, as an HIV-positive woman named Marie attests. The 52-year-old grandmother of four has been living with the disease since she was raped at gunpoint in 1987.

But she doesn’t pretend that it’s easy. Even though the public is more informed than they were two decades ago, many HIV/AIDS patients say they still bear a stigma.

“Everybody doesn’t look at it the same way,” Marie says. “You get a lot of criticism. Very few friends and my family know, and they were more supportive than I thought. I kept it away from my kids for quite some time.”

Fortunately, new treatments for HIV/AIDS are churned out at a swift rate. Thirty drugs are currently on the market, allowing infected people to lead increasingly normal lives.

“It’s been over 20 years for me and I’ve gone from worse to better,” Marie says.

Others aren’t so lucky — an estimated 16,000 people in the U.S. die each year from complications related to HIV/AIDS. Because of their weakened immune systems, HIV/AIDS patients are especially susceptible to infection with other pathogens, like Hepatitis C and tuberculosis.

The mystery of why some patients develop few complications while others fare much worse is a question scientists around the world are trying to answer. But the biggest concern of AIDS researchers in Florida is preventing new cases, particularly the transmission of disease from infected mothers to newborn babies.

Eight years ago, when Goodenow’s study first began, pregnant women infected with HIV had few therapeutic options. But recent advances in prenatal drug therapies have substantially decreased the rates of mother-to-child transmission.

The Centers for Disease Control and Prevention estimates that less than 2 percent of American mothers currently infected with HIV/AIDS will transmit the viruses to their babies during birth. Without the drugs, about 40 percent of infected mothers would give birth to babies with HIV.

Shared Effort

With so many facets to the AIDS problem in Florida, Goodenow has turned to colleagues at other institutions around the state for help. Since 2007, she has been spearheading a multi-institutional effort to establish Florida’s first Center for AIDS Research.

“HIV/AIDS is a significant public health problem in Florida,” Goodenow says. “As a state, we’re third in the country with the numbers of HIV/AIDS cases. There are at least 100,000 infected individuals that we know about.”

In 1988, the National Institutes of Health created a program called Centers for AIDS Research to support collaborations between basic scientists and clinicians, effectively bringing AIDS research from the lab bench to patients’ bed-sides. The NIH currently supports 19 centers at top-ranked institutions across the nation, including Harvard University, Duke University and Case Western Reserve University.

Florida researchers hope to establish CFAR number 20. The group is currently conducting preliminary studies that will pave the way for a formal application to the NIH.

If awarded, the Florida CFAR will be the first in the nation to harness the collective strength of more than three research centers. UF researchers are currently collaborating with HIV/ AIDS experts at eight other Florida institutions, including the University of South Florida, the University of Central Florida, Florida State University, the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Tampa General Hospital, Wolfson Children’s Hospital in Jacksonville, Merck & Co. Inc. and the Ponce School of Medicine in Puerto Rico.

In all, federal funding for HIV/AIDS research at the 10 institutions surpassed $8 million during the 2006 fiscal year. About half of that revenue was generated by UF researchers like Goodenow. With so many heavy hitters on the team, the organizers are hopeful the center will be funded.

In a speech at a recent CFAR planning session, Douglas J. Barrett, UF’s senior vice president for health affairs, said the center would provide an unprecedented opportunity for “Gators and Seminoles and Knights and Bulls to work together to do what’s right, in terms of the best investment of Florida’s dollars and Florida’s people.”

The group promises to do just that when they get their chance. A large arm of their research will study HIV/AIDS across the lifespan, with the goals of preventing new cases in the elderly and improving the quality of life for adolescents and older individuals affected by the disease.

HIV/AIDS in the Elderly

About 15 percent of Americans infected with HIV/AIDS are over 50, according to the CDC. Sexually-transmitted diseases in the elderly population have become increasingly problematic in recent years, thanks in part to performanceenhancing drugs such as Viagra. And because older couples often forego contraceptives, these diseases can spread quickly. The CDC estimates that Americans over age 50 will comprise half of all AIDS cases by 2015.

“Body changes that occur with AIDS are comparable to accelerated aging,” says Marco Pahor, director of UF’s Institute on Aging and chair of the College of Medicine’s Department of Aging and Geriatrics and a collaborator on the Florida CFAR initiative.

Much of the current knowledge about the aging process, including the factors that influence loss of skeletal muscle mass and strength, have originated from AIDS research, Pahor adds.

Marie, who plans to retire in a few years, says she hopes the research under way at UF will make her life easier as she heads into her golden years.

“It’s hard enough growing old,” she says, “But it’s a lot harder with HIV. You have to rearrange everything, even your diet.”

Watching her granddaughter play outside, Marie wonders when researchers will find a cure for the disease. Hopefully in her lifetime, Marie says. But if she doesn’t live to see a cure, she hopes her children will.

“You tell those scientists to hurry up,” she says. “Keep on working.”

Maureen Goodenow
Professor, Department of Pathology, Immunology
and Laboratory Medicine
(352) 273-8165