Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Reuters NewMedia - Thursday December 3, 1998
Maggie Fox, Health and Science Correspondent

The gene variant can make people progress from HIV infection to full-blown AIDS two years sooner than normal, the researchers at the National Cancer Institute said.

"We have shown there is a (gene) variant associated with more rapid progression," Dr. Mary Carrington, one of the researchers who worked on the study, said in a telephone interview.

Not everyone with this gene type progresses quickly to AIDS if they get infected. But the researchers estimate that 10 to 17 percent of patients who develop AIDS within 3.5 years of being infected do so because they have these genes.

The NCI researchers, headed by Dr. Stephen O'Brien and helped by scientists across the country, compared the genes of 474 healthy people and more than 1,300 infected with HIV.

They looked specifically at a gene known as CCR5, which controls production of a receptor, or type of cellular doorway, that HIV uses to infect cells. The specific variation they found is in what is known as a promoter gene, which influences CCR5.

"The variation is actually upstream of the gene itself," Carrington said.

"It's in what's called the promoter region. It's the region that directs transcription of that gene."

It is not clear exactly what is happening to cause people to develop AIDS faster, Carrington said.

"We don't know why but the most obvious thing to test, which is what we are doing, is that it enhances transcription of this gene."

In other words, the body produces extra copies of CCR5, which gives the virus even more doorways to get into cells.

Genes greatly influence the progression of HIV infection. Several variations have been found that help people resist infection. This is the first one to be found to speed up the development of AIDS.

Knowing about these differences can help scientists design better drugs to fight infection and perhaps even to prevent it.

This particular variation, known as CCR5P1/P1, only affects people if they carry two copies of the gene. An estimated seven to 13 percent of people do, Carrington's team reported in the journal Science.

Most of the people they looked at were white, but there were 162 blacks in the study whose HIV infection could be traced. Carrington said they did not seem to find the fast progression effect in blacks.

"We didn't see the effect clearly in African-Americans, which may have been because of the numbers," she said.

"It is possible that the same effect is not present in African-Americans." They will have to study more blacks to be sure. About seven percent of blacks and nearly 13 percent of whites carry both copies of the genes. Also, the effect is seen early on or not at all.

"If you happen to have that genotype but you don't progress to AIDS rapidly early on, later on it doesn't seem to make much difference," Carrington said. People vary greatly in how long it takes to develop AIDS after they are infected with HIV. Some develop AIDS very quickly, within two years, while others, termed long-term non-progressors, stay symptom-free 15 years later or longer. The median time to AIDS, defined by the development of the first "defining" disease such as the cancer Kaposi's sarcoma or pneumonia, is 10 years.

A cocktail of strong drugs can keep AIDS at bay for years.
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