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FEATURES
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UC DAVIS RESEARCHERS STUDY THE NEW FACE OF AIDS

Researchers examine how ethnicity and gender alter immune responses to HIV

 "" PHOTO — UC Davis microbiologist
Barbara Shacklett is studying histocompatibility antigens' role in HIV.
 
UC Davis microbiologist Barbara Shacklett is studying histocompatibility antigens' role in HIV.
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The history starts simply enough — with a year, 1978, and a blip on the nation's mortality statistics. "Deaths in the U.S. – 31."

In another year, those statistics tell us eight times as many people die. The next year, 30 times. The year after that, 80 times.

The U.S. Centers for Disease Control record a sudden rise in rare illnesses, such as Kaposi's sarcoma. Unusual statistics emerge: what appears to be a growing epidemic seems highly selective, attacking gay men, Haitians, intravenous drug users and a Canadian flight attendant with a foreign-sounding name — Gaetan Dugas.

Some people take comfort in the epidemic's foreignness. But, then, it hits home. The virus behind the plague — HIV — claims the life of rugged movie icon Rock Hudson. It infects basketball star Magic Johnson. A dentist transmits it to his patient, Kimberly Bergalis. Teenager Ryan White, a hemophiliac, garners global support as he gradually loses his fight against the disease.

Researchers and clinicians worldwide go into overtime, targeting studies, treatments and therapies toward the demographic group most affected by the crisis – Caucasian men in North America and Western Europe. Governmentfunded studies and news reports chronicled their successful efforts.

Minorities at risk

But now, nearly three decades, 16 million deaths and 34 million infections later, AIDS — largely contained among white Western males — is the leading cause of death among young African-American men and a significant health threat to Latinos and minority women.

By the numbers:
In 2002, AIDS was the leading cause of death among African-American women ages 25-34 and the second leading cause of death for African-American men ages 35-44.
In 2002, AIDS was one of the top three causes of death for African-American men ages 25-54 and African-American women ages 25-44.
In 2004, the rate of AIDS cases in the United States among African-Americans was more than three times greater than the rate for Hispanics and more than nine times greater than the rate for Whites.
At the end of 2004, the Centers for Disease Control and Prevention (CDC) estimated that over 60 percent of women living with AIDS, and 43 percent of all people living with AIDS in the United States were African-Americans, the highest for any racial/ethnic group.
African-Americans accounted for 50 percent of all AIDS cases diagnosed in 2004 in the United States, yet African-Americans make up only 12 percent of the population.
In California, as of Nov. 30, 2005, there were 138,997 cumulative reported AIDS cases; 24,496 of these cases were African-Americans. This represents over 18 percent of all AIDS cases, yet African-Americans constitute only seven percent of California's population.


The California Department of Health Services and the National Center for Health Statistics
 
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This demographic shift has created differences in the care of HIV-infected populations that disturb and motivate UC Davis Health System clinicians and researchers who believe that disparities in medical care for diseases such as AIDS should be studied, analyzed and corrected.

To that end, UC Davis researchers Richard Pollard, Satya Dandekar, Barbara Shacklett and Donna DeFreitas are partnering with the California Department of Health Services Viral and Rickettsial Disease Laboratory in a multidisciplinary research consortium, the California Center for the Biology of HIV in Minorities.

"The information we are gathering in this project is vital in understanding if there are racial and gender differences that could be utilized to further tailor therapy to targeted groups," says Pollard, professor, chief of the infectious diseases division and the project's principal investigator.

Recent studies, Pollard explains, have revealed age differences "that led many of us to treat older individuals earlier in an attempt to restore as much immune function as possible. If we discover similar results in this project, our findings could result in changes in clinical practice," he says.

The UC Davis/California Department of Health Services consortium is one of five HIV/AIDS collaborative centers funded by the University of California's university-wide AIDS Research Program.

Collaborative study

"This project nurtures collaborative interactions among basic scientists with expertise in HIV virology, immunology and molecular biology, and clinical researchers with expertise in HIV therapy and clinical care," says Dandekar, professor and chair of the Department of Medical Microbiology and Immunology, who is director of the pilot project core.

 "" PHOTO — UC Davis microbiologist
Barbara Shacklett is studying histocompatibility antigens' role in HIV.
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Shacklett, a microbiology and immunology assistant professor, agrees. "UC Davis is in a unique position to develop these types of studies. We have a wonderful clinical team and a long history of research on HIV, beginning in the 1980s when Murray Gardner led the first NIH-funded Center for AIDS Research here."

The consortium team is studying several hundred African-American, Latino and female HIV patients at the UC Davis Center for AIDS Research Education and Services (CARES) in Sacramento, looking at how immune responses differ between ethnic groups and how women respond to treatment differently than men.

"The project is designed to identify how ethnicity and gender alter immune responses to HIV," explains Pollard. "No one has ever systematically examined these issues."

Immune system differences

One issue of interest to Shacklett is how so-called "histocompatibility antigens" direct the immune system's "killer T-cells" to attack and kill HIV-infected tissues.

"We see some differences in the prevalence of certain histocompatibility antigens based on race and ethnicity," Shacklett says. "This is just one example of an inherited trait that may influence the immune response to HIV, and lead to better or worse outcomes." At the same time, Shacklett says, "physicians also need to take gender into account when prescribing medications and dosages for AIDS patients."

Pregnancy and increased sensitivity to certain anti-viral medicines affect female HIV patients in unique and clinically significant ways that researchers and caregivers need to understand, explains assistant professor and infectious disease specialist Donna DeFreitas.

Helping minority women

"Worldwide, HIV has become largely a disease of minority women," DeFreitas says. "Research looking at treatment response differences is extremely important if we are to address HIV, not just in our own community, but also in the global community."

PHOTO — UC Davis infectious disease researcher Donna DeFreitas wants to better understand the effects HIV drugs have on female HIV patients.  ""

UC Davis infectious disease researcher Donna DeFreitas wants to better understand the effects HIV drugs have on female HIV patients.
 
   

DeFreitas knows something about the world community. As a child in her native Trinidad, she came with her family to the U.S. for "a better life," later establishing herself as a polymath who excelled at the science of research and the necessary art that the best physicians bring to patient care.

In addition to the research she conducts, DeFreitas expressed her passion through a two-act stage play. For multiple evenings in the summer of 2003, DeFreitas joined UC Davis audiences to watch performances of "The Life Play," a grantfunded play she wrote to express the choices, decisions and education of African-American women "dealing with HIV in their life."

"Act 1 was about a woman dying of HIV and another woman finding out she's infected while she's pregnant," DeFreitas said. "In Act 2, we saw a woman negotiating with her partner, a prostitute learning to limit her risk, and a girl refusing to have sex without a condom."

Passion drives research

Passions like DeFreitas' for the many faces and facets of AIDS inform and inspire the entire UC Davis team. "We have benefited from an excited core of people who desire to explore novel avenues while building on traditions of excellent clinical care," DeFreitas explains. "Our research foundations are largely secondary to the passion and enthusiasm of our people."

Shacklett feels a similar passion. "I lost several personal friends to AIDS during the early years of the epidemic and initially that is what motivated me," she says.

"Now that I see AIDS spreading throughout the world, as well as to understudied populations in our own country, I feel it is more urgent than ever to develop multidisciplinary, collaborative research studies. We have the tools to understand and limit the spread of HIV, but that won't happen without a lot of hard work."

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  "UC Davis is in a unique position to develop these types of studies. We have a wonderful clinical team and a long history of research on HIV, beginning in the 1980s when Murray Gardner led the first NIH-funded Center for AIDS Research here." — Barbara Shacklett  
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