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AIDS Interrupted

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When molecular virologist Julie Overbaugh(PhDChem’83) first touched down in Kenya in 1993, the HIV epidemic was in full swing, with 9 million people in sub-Saharan Africa infected —14 million worldwide — and new infections among women and newborns ravaging the continent.

It had been a decade since U.S. Health and Human Services Secretary Margaret Heckler had promised an AIDS vaccine within two years. But despite the work of doctors and nurses on the ground in Africa and scientists in labs at distant research institutions, that goal remained elusive, as it does today.

“There were a lot of things we thought we knew back then, but in retrospect we did not,” recalls Overbaugh, who first traveled to Kenya to help set up experiments looking at blood samples from HIV-exposed women and their infants.

There, the young scientist in the crisp white lab coat witnessed gravely ill women crowded into sweltering, open-air courtyards, waiting for hours to be seen in clinics with no proper exam tables and no running water. Many clutched babies for whom the future was uncertain.

“It was really striking, knowing that a lot of those babies were likely to be HIV positive, and there was really not much that could be done for them,” recalls Overbaugh, who had spent years studying public health but had never visited a developing country. “I was able to see, firsthand, the magnitude of the problem. That was very motivating for me.”

Fast forward two decades and Overbaugh, a member of the Fred Hutchinson Cancer Research Center and affiliate professor at the University of Washington, is credited for not only advancing the understanding of how HIV is transmitted and how to halt that transmission, but also for bridging the chasm between basic laboratory scientists and on-the-ground clinicians in the world of HIV research.

The two research projects she helped launch in 1993 have grown to include thousands of samples that continue to provide insight into how HIV operates and inform vaccine development.

“The kind of translational, multidimensional research projects she set up in the early 1990s were at the time very unique,” says Scott McClelland, a trained medical doctor and an HIV researcher at the University of Washington. “Through them, she has helped us characterize which viruses tend to be transmitted and better understand the immune response to infection. I feel unbelievably fortunate to work with her.”

Growing up in a working-class community in Pennsylvania, Overbaugh had no dreams of being a scientist.

“I didn’t even know what scientists did,” she recalls. “But I was good at science.”

The daughter of a lumber salesman and a mom who stayed at home while her kids were young, she was recruited to play basketball at the University of Connecticut. She attended CU-Boulder for a doctorate in biochemistry and the Harvard School of Public Health for a fellowship. Her longing to put her lab skills into a setting where she could “change lives” landed her at University of Washington, just as it was developing its HIV research program.

At the time, she recalls, most of the basic research on HIV was being done in isolated labs at western institutions where scientists pored over lab-grown versions of the virus to see how it impacted cells in culture. Many assumed that “one HIV was just like another HIV,” and that often led to “wrong conclusions.” In Africa she had an opportunity to study how the multiple strains infecting people operated in real time.

We stepped into the middle and tried to answer real-world questions with basic science,” she says.

In doing so, she found herself going between the bustling capital and humid coast of Kenya. In the coastal city of Mombasa, University of Washington professor Joan Kreiss had established a study of women at risk for HIV. In the crowded capital city of Nairobi, another clinic offered HIV tests for women and children to understand the risk of breast milk in HIV transmission.

Julie Overbaugh (PhDChem’83) has published 200 papers, trained dozens of Kenyan scientists and heads up an international team of researchers and doctors who work together across two continents to battle HIV/AIDS. © Stefanie Felix, courtesy of Fred Hutchinson Cancer Research Center (FHCRC).

Overbaugh’s role was to collect, store and study blood samples in makeshift labs near the clinics. The conditions were much different than what she was used to at home.

“The power might go out five times a day when you were trying to do experiments,” she recalls, and storing samples in the African heat with unreliable refrigeration was tricky.

But her experiments in her lab using these samples yielded important discoveries.

By studying thousands of samples from HIV-positive moms and their newborns, the team determined that babies who breastfed from infected moms were more than twice as likely to get HIV than those who did not breastfeed.

They also gained insight into when and how that transmission occurred, which is mostly in the first three-to-six months of life. This created a foundation that helped shape the studies of the timing of anti-retroviral medication. Today, according to the Elizabeth Glaser Pediatric AIDS Foundation, nearly half of pregnant women and 42 percent of HIV-exposed infants in developing countries receive medications to keep the virus from moving from mom to baby.

The other ongoing study has looked at thousands of samples from Mombasa sex workers to answer fundamental questions. Of the many different variants of HIV, which ones are most likely to be transmitted? And does contracting one version of HIV keep people from getting another version?

The answers, while useful, have been “disheartening,” says McClelland, noting that HIV is an “exceptionally hard” virus to create a vaccine for because there are so many different variants. “The genetic diversity is beyond the scope of anything we currently vaccinate for.”

For a time researchers hoped that infection with one version might prompt immunity to a second. But according to Overbaugh’s research, that is unlikely.

“What we have been finding is that at least the levels of antibody you get in natural infection are not protective [against other versions of the virus],” she says. “That is not good news.”

Overbaugh and her colleagues are now looking at the immune response of “superinfected” patients [those with more than one strain of HIV] to see if they may produce a stronger antibody response that could inform vaccine design. Thus far, the idea looks promising, with some of the superinfected women exhibiting “a broad and potent ability to neutralize a wide variety of strains of HIV over a sustained period of time,” she says.

Still, Overbaugh doesn’t anticipate an HIV vaccine to be unveiled in the next five years.

In the meantime, she’ll continue to travel to Kenya once a year to help oversee and design research studies and bolster lab facilities. In the United States she trains Kenyan scientists, so they can return to Africa to carry on the research.

“In the long term, they are the ones who are most likely to solve this problem,” Overbaugh says. “Your perspective is very different when you are in the midst of an epidemic than when you are in an ivory tower thousands of miles away thinking about it.”

HIV/AIDS by the numbers An estimated 34 million people worldwide are living with HIV. Sixty-eight percent of them live in sub-Saharan Africa. Each day, HIV/AIDS infects 7,400 new people and causes 4,900 deaths worldwide. More than 1,000 children under age 15 are infected with HIV every day, mostly as a result of mother-to-child transmission of the virus. Approximately 17 million women were living with HIV in 2010, up from 13.8 million in 2001. In 2010, 1.8 million people died of AIDS-related illness. Approximately 67 percent of them lived in sub-Saharan Africa.

Photo (center) courtesy of Fred Hutchinson/Cancer Research Center