HIV Progression Linked To Genes

(As reported 3/12/99)
Inherited genes may explain why some people infected with HIV develop AIDS quickly, while others live with the virus for years in relatively good health, scientists report.

In a study published Friday in the journal Science, researchers at the National Cancer Institute say differences in the inherited pattern of what are called HLA Class I genes appear to determine who gets sickest soonest after an HIV infection.

The discovery, based on a genetic analysis of 500 HIV patients, has no immediate medical application, but it increases understanding of how the virus attacks the body, said Mary Carrington, lead author of the study. That knowledge could lead to better drugs or vaccines against the virus, she said.

Carrington said there are three different HLA Class I genes, identified as A, B and C. People inherit two copies of each of the genes. This means they can have as many as six unique combinations or as few as three.

"The more different forms of this gene a person has, the more resistant that individual is to progression of the disease," said Carrington.

An HIV infection in people with non-matching HLA Class I gene pairs, for instance, may not progress to AIDS for six to 12 years, the researchers found. Those who inherited matched pairs of the genes tend to develop AIDS in three years or less.

HLA Class I genes are part of the immune system. Their job is to identify cells that are infected with the virus and to leave a signal molecule on the surface of the infected cell. Another part of the immune system, the cytotoxic T-cell, will kill cells marked by the signal molecule, thereby blocking the spread of the virus.

The HIV virus is constantly changing and eventually will find a form that is not recognized by any of the HLA Class I genes, Carrington said.

If an individual has a variety of HLA genes, it takes longer for the HIV to develop changes not recognized by the immune system. For this reason, she said, a person with a variety of gene forms will avoid AIDS longer.

Carrington said about 40 percent of the people examined in the study had a gene pattern that promoted a slow disease progress, while about 45 percent had a gene combination that led to rapid progression.

Each of the three HLA genes has many alleles, or forms, that differ only slightly from each other. For instance, there are about 200 different forms of the HLA-B gene, Carrington said.

The researchers found that people with paired copies of two of the gene forms, identified as B35 and Cw04, tended to progress to AIDS most rapidly.