Genetic Variation Associated With Survival Advantage in African Americans With HIV

From the start of the HIV epidemic, it appeared that some of the people who were infected with the virus were able to ward off the fatal effects of the disease longer than others. Recent studies have begun to unravel the cause of this phenomenon, and new research suggests that African Americans with the disease have a unique survival advantage if they have both a low white blood cell count (known as leukopenia) and a genetic variation that is found mainly in persons of African ancestry. This study was prepublished online today, in Blood, the official journal of the American Society of Hematology.

The research showed that African Americans with HIV who possess both a variation in the gene for the Duffy antigen receptor for chemokine (DARC) and leukopenia have slower HIV-to-AIDS progression rates than HIV-infected European Americans with leukopenia. Previous studies showed that the same DARC variant conferred protection for persons of African ancestry against a particular form of malaria, and that persons of African descent have, on average, lower white blood cell (WBC) counts than persons of European ancestry. Leukopenia is one of several blood conditions observed frequently in patients with HIV-1 infection, but its impact on disease course is relatively unknown.

"Even though leukopenia is tied to both African ancestry and faster disease progression, we found that compared with European Americans, African American patients with HIV who have leukopenia do not necessarily experience this expected outcome," says lead author Dr. Sunil Ahuja, MD, of the Veterans Administration (VA) Research Center for AIDS and HIV-1 Infection and the University of Texas Health Science Center in San Antonio.

This study evaluated data from the Air Force subset of the U.S. Military's HIV Natural History Study and included genetic and clinical data from 1,132 participants. The researchers tested for the presence of the DARC variation and evaluated patients' WBC counts from diagnosis and throughout the course of the disease to determine the impact of different levels of WBC counts on survival rates. The prevalence of leukopenia at the time of diagnosis was significantly higher in African Americans (28 percent) than in European Americans (15 percent) or other ethnicities (13 percent). The average WBC counts were also significantly lower during the course of the disease in African Americans with HIV than in other ethnicities.

The researchers found that leukopenia was generally associated with a faster disease progression from HIV to AIDS, independent of known predictors of AIDS development. "On average, leukopenic European Americans progressed nearly three times faster than their non-leukopenic African or European counterparts," explains Dr. Hemant Kulkarni, MD, first author of this study. "However, leukopenic African Americans had a slower disease course than leukopenic European Americans, even though twice as many African Americans in the study had leukopenia."

The investigators found that the DARC variation, not race, explained the differences in WBC counts in African Americans with HIV. Among those who were leukopenic, only those with the DARC variation experienced a significant survival benefit. Additionally, this survival advantage became increasingly pronounced in those with progressively lower WBC counts, suggesting that the interaction between DARC and WBC counts was the primary influence on slowing HIV disease progression in African Americans.

"The results of this collaborative study highlight the importance of accounting for other factors, such as the white blood cell count, to uncover the full effects of genetic variations that may influence HIV disease course," says Capt. Gregory Martin, MD, United States Navy, program director for the Infectious Diseases Clinical Research Program (IDCRP) and an expert on infectious diseases who was not involved with the study.

"White blood cells are intricately linked to inflammation, and inflammation is known to fuel HIV disease progression. Thus, future studies will need to decipher whether the interaction between the DARC variant and low white blood cell counts results in a reduced inflammatory state," says Dr. Vincent Marconi, MD, of the IDCRP.

The U.S. Centers for Disease Control estimates that about 1 million people in the United States are living with HIV or AIDS, and that about 60,000 individuals are infected with HIV each year.

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Blood Donations in U.S. Testing Positive for Chagas' Disease

In the 10 months since the U.S. Food and Drug Administration licensed the first blood-screening test for Chagas' disease, some 241 blood donations in the United States have tested positive, indicating donor exposure to the parasite known to cause this serious and potentially fatal parasitic infection, according to data released today at the annual meeting of American Association of Blood Banks (AABB). The test is manufactured by Ortho-Clinical Diagnostics, Inc.

Chagas'-positive donations have been reported in 34 states with the highest concentration in California, Florida and Texas, according to data compiled by the AABB.

Also called American trypanosomiasis, Chagas' disease is an infection caused by the blood-borne parasite Trypanosoma cruzi, or T.cruzi. The disease is endemic to most countries in Central and South America, as well as Mexico. Transmission occurs through insect bites, blood transfusions, organ transplants and via infected pregnant women to children in utero.

Early infection is usually mild and unrecognized, but persists lifelong and may lead to organ damage, particularly of the heart and esophagus, causing an estimated 50,000 deaths annually worldwide. Infection also can be severe in people whose immune systems are suppressed, such as organ transplant recipients.

During presentations at the conference today, blood safety experts also say they are investigating new cases of transmissions of Chagas' disease that may have occurred through blood transfusions and via insect bites from bugs known to carry the parasite. Such cases have been extremely rare, or have gone undocumented, in the United States. Dr. Susan Stramer, executive scientific officer for the America Red Cross, says blood safety experts are
investigating 20 cases of possible insect-to-human transmissions with strong evidence suggesting that nine cases may have occurred in the U.S. Also, the Red Cross is investigating four possible transmissions via blood transfusions. Details of these cases were not disclosed.

"While we have known that Chagas' disease was present in North America, the numbers of Chagas'-positive blood donations, as well as new reports of transmission of infection to persons from bugs, are surprising," says Dr. James Maguire, M.D., director, International Health Division, University of Maryland School of Medicine. Maguire is the former chief of the parasitic
diseases branch at the U.S. Centers for Disease Control and Prevention (CDC).

The American Red Cross was among the first blood collection agencies in the U.S. to begin testing donations for Chagas' in late January, following FDA approval of Ortho's blood-screening test in December 2006. Today, approximately 70 percent of all blood donations in the U.S. are now being screened for Chagas'.

In additional developments, public health authorities in the state of Arizona have made Chagas' a "reportable" disease. Three southern states are considering similar action. A reportable disease is one that must be reported to federal, state, or local health officials when diagnosed --
like active tuberculosis, hepatitis, gonorrhea and HIV, for example.

According to the CDC, as many as 8 to 11 million people in Mexico, Central America and South America have Chagas' disease. Most do not know they are infected. Chagas' disease can be treated successfully if detected soon after the infection occurs, but there is no cure once the
disease has entered the chronic stage.

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