AIDS Weekly (07.14.03) - Friday, August 22, 2003
In the first application of a novel statistical technique to
the study of disease, researchers found that the genes
underlying HIV infected patients' immune systems can predict
their risk of progressing to AIDS. Analysis showed that the
virus is less likely to progress in patients bearing rare
immune system gene variants than in those with more common
Thomas Kepler, PhD, interim director of Duke University's
Center for Bioinformatics and Computational Biology, part of
Duke's Institute for Genome Sciences and Policy, said the
finding clarifies the interaction between HIV and patients'
immune defenses and provides information that may ultimately
help doctors tailor treatments to individual patients.
"Specific combinations of alleles [variations of a gene that
differ slightly in structure and function] that humans carry
appear to protect against HIV," Kepler said. "HIV-infected
people who carry particular, rare gene variants have much
lower viral loads than other patients do."
The study focused on 996 men, 562 of whom were HIV-positive,
enrolled in the Chicago component of the Multicenter AIDS
Cohort Study. The researchers genetically screened
participants' blood samples for two immune system genes, human
leukocyte antigen A and B (HLA-A and HLA-B). HLA molecules
orchestrate the response of T cells; the many different HLA
alleles have different biological activities that affect the
body's response to invasion.
Immune system alleles are notoriously diverse, and Kepler and
colleagues were having trouble identifying gene combinations
that affect disease outcomes using traditional methods. They
devised a novel statistical method, minimum description length
(MDL), to divide patients into disease progression groups in a
more detailed manner. "The method allowed us to exhaustively
go through all possible gene partitions and assign a score to
each, while avoiding the pitfalls of traditional methods of
analysis," Kepler explained. This research represents the
first time MDL has been used to analyze biomedical disease-
The statistical classification of the patients revealed that
"greater protection against HIV was afforded by rare immune
system alleles," according to Kepler. "That suggests that HIV
has adapted to attack the dominant alleles in the population.
In other words, the virus goes after the bigger target."
Screening patients' immune systems, physicians might
ultimately be able to identify patients at the greatest risk
for progressing to AIDS and prescribe treatments accordingly.
Study leaders Elizabeth Trachtenberg of Children's Hospital
Oakland Research Institute, Calif.; Bette Korber of Los Alamos
National Laboratory, N.M.; and Steven Wolinsky of Northwestern
University, Ill., were among those who joined Kepler in the
collaborative effort. The study, "Advantage of Rare HLA
Supertype in HIV Disease Progression," appeared in Nature