How ironic it would be if the solution to the HIV/AIDS problem came from outside the HIV/AIDS research industry. Some new areas of medical science are presenting precisely this possibility.
What’s so exciting about this development? Research in one area of science that results in unexpected advances in other science areas are often relatively free of the politics that hold back the beneficiary science. In the case of HIV/AIDS, the political push to introduce male circumcision promises to slow the progress in behavioral change and the roll out of proven prevention techniques and technologies.
The numerous new developments in HIV/AIDS research of the past 18 months is even greater reason to proceed cautiously or not at all on male circumcision. The discovery of very precise genes that control HIV in long term survivors and those immune to infection is a clarion call to rethink the last-resort measure of genital surgery.
Fair use article after the jump.
Study sees hope for controlling new HIV cases:
Genetic advance is spin-off of Human Genome Project
Duke University scientists, following the genetic road maps laid out by the Human Genome Project, have discovered variations in three genes that might help people newly infected with HIV control the virus in the years before they develop AIDS.
The discovery is the latest in what has been described as an “avalanche” of new findings about how specific genetic variations are linked to conditions ranging from obesity and heart disease to breast and prostate cancer.
It is a feat made possible by the huge effort to map the entire Homo sapiens genome, the 25,000 genes that carry the coded instructions for making and maintaining a human being.
A rough outline of the genome was completed in June 2000. Six years later, scientists reported that they had decoded, with a high degree of precision, the sequence of more than 3 billion base-pairs of DNA — the letters that make up the entire text of the human blueprint.
New high-speed machines developed in Silicon Valley and San Diego are allowing scientists to scan an individual’s entire set of genes for subtle variations and, by comparing hundreds of such scans, detect whether these different gene traits are associated with health problems.
Thursday’s study, published in the online edition of the Journal Science, is the first to apply the new genome-scanning technology to an infectious disease.
“What we are seeing here transcends the study of HIV,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. These “genome wide association studies,” he said, will probably yield insights into how germs make people sick and how to treat and prevent diseases.
The Science study involved researchers from seven countries, led by Duke’s Center for HIV/AIDS Vaccine Immunology, a federally funded institute where researchers are attempting to uncover what immune system traits are necessary to prevent or control infection by HIV, the virus that causes AIDS. Identifying those traits could be a key to finding an effective AIDS vaccine.
“We’re trying to understand why some people are better able to handle the virus than others,” said David Goldstein, director of the Center for Population Genomics at Duke, and lead author of the Science paper. In the latest experiment, researchers pooled information on 30,000 HIV infected patients. From this group, the scientists selected 486 patients whose medical records and conditions made them ideal candidates for study.
The focus of the research was on the viral set-point — a level at which the concentration of virus in an individual’s bloodstream becomes stable. The set-point can vary enormously among patients. Some have only a few hundred particles of virus per milliliter of blood, others have hundreds of thousands. Those with the lowest levels are usually better able to control HIV.
The Duke scientists scanned the genes of the 486 subjects to see if they carried any of 550,000 gene variants commonly found in the human population, and then analyzed the data to see if a relationship existed between those genetic differences and different ability to control the virus.
Out popped two genes: one called HLA-B*5701 and another called HLA-C.
The two genes together accounted for 15 percent of the differences in the viral set-points of the 486 patients, according to the Duke analysis. Although that percentage may seem minor, Goldstein said, “it is highly unusual to have this much variation explained by genetics.”
Variants of the HLA-B gene had already been spotted in studies of a few hundred HIV-infected people known as “elite controllers,” who are able without drugs to keep their viral loads below levels detectable in standard tests.
The gene normally helps infection-fighting white blood cells destroy other cells that have been hijacked by viruses — such as HIV — thereby limiting the spread of the invading microbes. In most patients, however, HIV has the ability to shut-down the HLA-B gene.
The HLA-C gene had never been linked to AIDS before, and is intriguing because HIV cannot shut it down. The gene produces a protein that resides on the surface of white blood cells, and people with the variant form seem to be able to produce more of that protein — possibly explaining why they have lower levels of virus. “Everyone carries HLA-C, but in varying amounts,” Goldstein said. If someone could figure out a way of cranking up the activity of HLA-C, it might be the basis for an effective AIDS vaccine.
The study also fingered a third suspect gene, ZNRD1, which might inhibit the ability of HIV to replicate.
New gene-reading machines produced by Illumina Inc., of San Diego, and Affymetrix Inc., of Santa Clara, are speeding the development of genome-wide analysis. Both companies make equipment that scans for specific sequences of DNA in liquefied samples of genetic material from a patient.
Those target sequences were selected by an international consortium of researchers, which analyzed genomes of more than 200 individuals around the globe, looking for similarities and differences. The result is the list of the 550,000 common genetic mutations that serve as reference points across of the vast expanse of the human genome. Gene machines can scan for each of those variants simultaneously.
Sometimes these genetic mutations are directly responsible for an unusual trait; more often they serve merely as markers — like a red tree in a forest of green trees — that tell scientists that something unusual may be occurring in genes located nearby.
Dr. Eric Topol, a cardiac surgeon who heads the Scripps Genomic Medicine Institute in La Jolla, said genome-wide analyses are vastly more powerful than earlier techniques meant to find genetic links to disease.
Previously, researchers would have to identify a suspect area on a chromosome, and conduct exhaustive studies, screening to see if there was a link between the disease and the single gene.
“That was in the old days … just a few years ago,” Topol said.
Now, the entire human genome can be scanned at once, and scientists are finding links to genes they had no suspicions were connected to disease.
Russell, Sabin. Study sees hope for controlling new HIV cases: Genetic advance is spin-off of Human Genome Project. San Francisco Chronicle [sfgate.com]. July 20, 2007.