Genetic Variation May Raise AIDS Infection Risk in Africans

from Bloomberg

By John Lauerman

HIV risk may jump 40 percent in people of African ancestry because of a slight genetic change, according to researchers who say the mutation might help account for the spread of AIDS virus in Africa.

The gene variation may explain as much as 11 percent of all cases of the disease on that continent, said an international team led by Weijing He, an infectious-disease researcher at the University of Texas Health Science Center at San Antonio. In a paradox, the variant also appeared to slow the progress of AIDS in infected people, the scientists said in a study that will be published tomorrow in the journal Cell Host & Microbe.

About three-quarters of the 33 million people worldwide who are infected with HIV, the virus that causes AIDS, live in Africa south of the Sahara, where most people are black. The gene variation may provide a clue as to why the virus has spread so much there, as well as among people with African heritage living elsewhere, said Robin Weiss, a University College London virologist who helped write the study.

``It's the first inherited genetic factor that's African- specific shown to increase the risk of the HIV,'' he said yesterday in a telephone interview. ``At least a portion of the burden of the disease in Africa is because people there are born more susceptible to the virus.''

While blacks account for about 13 percent of the U.S. population, about half of people living with HIV in that nation in 2005 were black, according to the Centers for Disease Control and Prevention, based in Atlanta.

New Understanding

The study gives researchers a new depth of understanding about HIV's spread through populations and the body, said Catherine Hankins, chief scientific officer for UNAIDS, the United Nations agency that coordinates AIDS prevention and care.

``This is a whole new world that we couldn't have accessed five years ago,'' she said yesterday in a telephone interview. ``What this suggests is that we need to look even deeper at host genetics and susceptibility to HIV.''

The researchers also stressed that genes are just one of many factors involved in the relatively high rates of HIV among Africans and U.S. blacks.

``There are many social issues, such as poverty and lack of access to health care, that contribute heavily to the risk of HIV,'' said Sunil Ahuja, a University of Texas Health Science Center professor of medicine who helped write the study, in a telephone interview. ``If you take care of those, you can go a long way toward reducing the risk of HIV.''

Single Letter

The explanation for how a small genetic change, involving a single letter in the 6-billion-letter DNA code, can raise the risk of HIV infection in those exposed, usually through blood or semen, centers on a protein called DARC, or Duffy antigen receptor for chemokines.

Chemokines are chemical messengers that normally attach to red blood cells, immune cells and nerve cells. HIV gets into cells by attaching to a protein on immune cells, called CCR5 that is normally reserved for chemokines.

About 90 percent of Africans carry a mutation that stops red blood cells from making DARC, the chemokine receptor, on their surfaces. The gene variant may be so widespread among Africans because one form of malaria also uses DARC to infect red blood cells, and lacking DARC protects against the disease.

The absence of DARC may also lower the amount of chemokines in the bloodstream, Weiss said. That could leave CCR5 free to bind HIV, rather than the immune messenger chemical, and increase the chances of HIV infection, he said.

Missing DARC

Normally, researchers expect something that raises infection risk to speed disease progress. Still, a study of HIV patients in the U.S. military showed that those whose red blood cells make DARC -- because they don't have the mutation seen commonly in Africans -- die on average about two years sooner after diagnosis than those with it.

Because of HIV's similarity to chemokines, the virus may also be able to bind to DARC, Weiss and Ahuja said. DARC's presence on red blood cells may give the virus a shelter in the bloodstream, enabling it to travel to new infection sites. Weiss called the explanation ``speculative.''

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