Genetic variation helps ward off AIDS.

Diversity is good. That's not a politically correct conclusion but a medical one. Scientists have begun to study how people's genetic variation may slow the speed at which an HIV infection leads to AIDS (SN: 8/16/97, p. 103).

"A few years ago, we really didn't have any genes that we knew influenced the outcome of an infectious disease. Now, we have a handful," says Stephen J. O'Brien of the National Cancer Institute in Frederick, Md., a leader in the effort.

In the March 12 SCIENCE, O'Brien and his colleagues report that HIV-infected people with a limited repertoire of so-called HLA genes are likely to develop AIDS within 3 to 5 years rather than the usual 10 or so. The researchers also found a quicker progression to AIDS in people having either of two particular HLA genes, even if they have diversity within their HLA genes.

HLA genes encode proteins that help cells present pieces of invading viruses or bacteria as targets for the immune system to attack. Each of the dozen or so HLA genes that people carry comes in many slightly different forms, or alleles. Some of these genes have more than 100 alleles. People typically inherit different HLA alleles from each parent, but a mother and father occasionally pass on the same HLA allele. Those cases, known as HLA homozygosity, seem to pose a threat.

Scientists have long suspected that having a diverse set of HLA genes allows people to present a wider range of targets to their immune system, but finding proof was tough. O'Brien's group now has examined the variation among three HLA genes (A, B, and C) in nearly 500 HIV-infected people. Those with different forms of all three genes--adding up to six different HLA alleles--avoided AIDS on average for 10 to 12 years, and many stayed healthy even longer. "If you're optimally represented with HLA types, you'll have a better defense against a virus that changes a lot, like HIV," concludes O'Brien.

He's now studying why having at least one of the HLA alleles called B*35 and Cw*04, even if the person isn't homozygous for it, makes one vulnerable to rapid AIDS progression. Since almost half of the population is homozygous at one of the three HLA genes or has a B*35 or Cw*04 allele, O'Brien says it's crucial to know how these genes influence HIV infections.

Identifying such genetic factors, he adds, should help in the evaluation of new AIDS drugs and vaccines. People who don't respond may have a vulnerable genome.