A study of HIV-positive and HIV-negative people, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH; both Bethesda, Maryland), has found that people with more copies of a certain gene that helps to fight HIV are less likely to become infected with the virus or to develop AIDS than those of the same geographical ancestry, such as European Americans, who have fewer copies of the gene.
Those findings could lead scientists to a screening test to determine the number of copies a person has in order to determine if earlier treatment might be necessary in some patients infected with HIV.
"There are a couple of potential uses at least for this line of research, and one is that it would allow you to make a more accurate prognosis about clinical outcomes in people with HIV infection," Matthew Dolan, MD, of the U.S. Air Force's Wilford Hall Medical Center and Brooks City-Base (San Antonio), told Diagnostics & Imaging Week.
Dolan said, "It would let you, just like a viral load measurement does, be able to say at a certain point, what the rate at which somebody might reach clinical endpoints is. It might let you down the road, for example, be able to tailor therapy better."
Currently, there is a "one size fits all" approach to HIV treatment, he said. Unfortunately, "immune responses have great variation." Such a test might indicate who could begin therapy earlier, and those patients who could wait until later. Based on the study, those with fewer copies of the gene would possibly need therapy sooner, because they may be more likely not only to contract the HIV infection, but also more likely to have a worse prognosis.
"We don't know that is the case, but that's an area down the road that might prove to be fruitful," Dolan said.
In addition to the screening test for individuals, Dolan and his fellow researchers are also interested in determining if "there is a role for evaluating HIV vaccines with this test."
Dolan, along with co-senior author Sunil Ahuja, MD, of the University of Texas Health Science Center and the Veterans Administration Center for AIDS and HIV-1 Infection (also San Antonio), focused on the gene that encodes CCL3L1, which the NIH called a "potent HIV-blocking protein that interacts with CCR5." CCR5 is a major receptor protein that "HIV uses as a doorway to enter and infect cells," the NIH said.
It was Ahuja's years of study in the area of chemokines and chemokine receptors that led the researchers to focus on CCL3L1, Dolan said. Ahuja had been successful in adapting an assay developed by someone else to a point where he was able to "correctly measure the number of copies of this gene on a single chromosome," he said.
"With that technical advance, then we were able to match that up with the genetic epidemiology and really study the impact in a cohort," Dolan told D&IW. "And there we see that there is prognostic information both in time to disease progression in people who are infected, but also in the ability to become infected in the first place."
That, in a nutshell, is the "new and novel" aspect of their findings, he said.
"There's been a lot that's been written about duplication of genes in human disease, but as far as I know, this is the first one that deals with susceptibility to an infectious disease," Dolan said.
The researchers analzyed blood samples from more than 4,300 HIV-positive and HIV-negative people of different ancestral origins to determine the average number of CCL3L1 gene copies in each group. The study included a cohort of HIV-infected individuals in the U.S. Air Force that have been followed since the mid-1980s. For example, they found that HIV-negative African-American adults had an average of four CCL3L1 copies, while HIV-negative European- American and Hispanic-American adults averaged two to three copies, respectively.
The NIH said that this does not mean that European-Americans are more prone to HIV/AIDS than other populations. Rather, using the average CCL3L1 gene copy number as a reference point for each group, the authors found that individuals with fewer CCL3L1 copies than their population's average were more susceptible to HIV infection and rapid progression to AIDS. People with greater-than-average CCL3L1 gene copies, in contrast, were less prone to infection by HIV or to rapid progression to AIDS.
Depending on the study population, each additional CCL3L1 copy lowered the risk of acquiring HIV by between 4.5% and 10.5%. Additionally, below-average CCL3L1 copy numbers were associated with a 39% to 260% higher risk of rapid progression to AIDS.
While the study findings suggested that some people are more susceptible to HIV infection than others, the authors aren't suggesting that those individuals can engage in risky behavior and avoid AIDS.
"We're talking about changing the odds, but not a barrier," he said, adding later that "it's a relative risk in a population for an individual it's not an overwhelming protective effect. It's a moderate effect."