Gene mutation increases risk of HIV infection

Times Staff Writers

A genetic mutation that originally protected Africans from a virulent form of malaria now renders them 40% more susceptible to HIV infections, offering a partial explanation for the disproportionate spread of the virus among Africans and African Americans, researchers reported today.

The mutation, however, has an unusual benefit. It also slows progression of HIV, the virus that causes AIDS, giving patients an extra two years of life, said Dr. Sunil K. Ahuja of the South Texas Veterans Health Care System, lead author of the paper in the journal Cell Host & Microbe.

The genetic variation is the first found to increase susceptibility to HIV and the first linked to people of African descent, said virologist Robin A. Weiss of University College London, a coauthor of the paper.

About 90% of Africans have the mutation, and it could account for as many as 11% of HIV infections on that continent, the researchers said. Sub-Saharan Africa accounts for about 75% of the world’s 33 million people infected with HIV.

The mutation also affects about 60% of African Americans and could partially explain why HIV is more common among blacks than whites in the United States. Blacks make up 13% of the U.S. population but account for nearly half of all newly diagnosed infections.


The study appears to confirm the theory that the risk of contracting HIV is not solely connected to behavior, said Phill Wilson, chief executive of the Black AIDS Institute, an HIV/AIDS think tank in Los Angeles.

“Black gay men’s behavior is no more risky -- and often less risky -- than white gay men, yet their vulnerability is so much greater,” Wilson said.

Ahuja cautioned, however, that social factors -- such as poverty, lack of access to healthcare and sexual behavior -- were probably more important contributors to the risk of HIV infection.

The mutation in question involves a single letter of DNA in the gene for a receptor found on the surface of red blood cells known as the Duffy antigen. Virtually all Caucasians have the antigen, but 90% of Africans and 40% to 50% of African Americans do not.

Because the malaria parasite Plasmodium vivax relies on the Duffy antigen to enter red blood cells, its absence offers protection against the disease. A precursor of P. vivax may have caused a lethal form of malaria thousands of years ago, which would have helped the mutation sweep through the population, researchers think.

Today, a different parasite, Plasmodium falciparum, is the predominant cause of the most fatal form of malaria.

Some laboratory research had shown that the Duffy antigen mops up HIV in the bloodstream, potentially reducing the likelihood that the virus can infect the immune cells that are its primary target.

To explore this possibility, the team studied the medical records and stored blood of 814 black Air Force personnel who were HIV-negative and 470 who were HIV-positive. The fact that all were servicemen eliminated many of the socioeconomic variables that might have confounded the analysis.

Researchers found that airmen without the Duffy antigen were 40% more likely to be infected with HIV -- and if they were infected, they lived longer by an average of two years. That surprised the researchers because typically anything that increases the risk of an infection is also likely to speed the progression of the resulting disease.

David Goldstein, a Duke University population geneticist who studies HIV genetics, said the unusual finding made him hesitant to embrace the result until it could be replicated in other studies -- a task he said he intended to pursue.

Goldstein added that African Americans, the subjects of the study, had an especially diverse genetic heritage that made it more difficult to link a particular gene to HIV susceptibility.

Ahuja said he and his colleagues did not know why the absence of the Duffy antigen increased HIV susceptibility and slowed progression of the disease. One possibility is that people without the Duffy antigen have lower levels of infection-fighting chemokines in their blood.

The lower levels make infection more likely. But once infection occurs, it may limit the amount of inflammation associated with the disease, minimizing damage to the body.