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KwaZulu-Natal, Durban | McCord Hospital
At home in Boston, Walker keeps a similarly demanding schedule as a researcher at Harvard Medical School, a clinician at Massachusetts General Hospital, and director of the Partners AIDS Research Center. The overarching theme of his research projects around the world is to learn more about how the immune system controls chronic viral infections such as HIV and to use that information to develop appropriate interventions at the bedside.
While still a postdoc, Walker was the first to identify cytotoxic T lymphocyte responses specific to HIV in infected persons, and these responses remain a major focus of his current research efforts. He and his colleagues have shown that early treatment of acute HIV infection leads to increased immunity and the transient ability to control viremia (the presence of virus in the bloodstream) in most infected persons but that the ability of the virus to mutate often allows it to escape immune detection in the first place. From more recent studies of infected patients from Boston to Africa, his group has shown that these mutations occur in a highly predictable fashion, indicating that there are constraints on the virus's evolution—something that Walker believes can be exploited in designing vaccines.
Walker's labs are now working on several projects, including a major new initiative to use genomic analysis to find out why certain individuals—called "elite controllers"—have immune systems that are naturally able to contain HIV and prevent the advent of AIDS. A related group consists of "viremic controllers"—infected persons whose immune systems also control the virus, though at slightly higher, but still barely detectable, levels of infection. Understanding how these controllers keep the virus at bay might offer a key to fighting HIV.
As part of these international efforts, Walker and collaborators are trying to identify 1,000 HIV-positive elite controllers and 1,000 viremic controllers worldwide. Finding and enrolling so many unusual individuals is no easy task; he estimates that among the more than one million HIV-infected persons in the United States, only about 2,000 are elite controllers. So far, the group has found a total of about 300 such persons around the world, but the search continues, with cooperating labs in Africa, Europe, Australia, China, North America, and Latin America.
Making use of the powerful sequencing facilities at the Broad Institute in Cambridge, Massachusetts, Walker and colleagues will compare genetic signatures of elite and viremic controllers with those of HIV-positive people whose bodies are unable to control the virus without the help of ARVs. "Our goal is to discover the molecular basis for these individuals' ability to coexist with the virus," says Walker. "If we can find a way to replicate it in others, we might be able to blunt the impact of the virus and slow or stop the HIV epidemic."
In South Africa, as with much of his life's work, Walker began with a scientific question—one that could not be addressed in the United States. "Why," he asked, "do children who become HIV-infected from their mothers do so much worse than adults who become infected?" While very few infected children were being born in the United States, large numbers of them were being born in Africa.
As his research programs became established in South Africa, Walker was able to help local collaborators make a major difference in patient outcomes. At St. Mary's Hospital, west of Durban, the iThemba Family Care Centre, established in 2002 by Walker's Partners AIDS Research Center with support from philanthropic sources, provides a high level of care to more than 2,000 people who are HIV positive.
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