August 7, 2007
Long-held theories on how HIV progresses to AIDS might be incorrect, according to a study published in the July 31 issue of the Proceedings of the Royal Society B, HealthDay News/Washington Post reports. The common belief among most scientists has been that various strains of HIV "battle a silent war within the body over time" until the fittest strain -- defined as the one that replicates itself the most -- "wins," according to HealthDay/Post. This strain "goes on to overwhelm" the immune system's cells and destroy the HIV-positive person's "defenses against disease," according to the theory, HealthDay/Post reports.
To test the theory, David Levy of New York University and Dominik Wodarz, associate professor of biology at the University of California-Irvine, used a mathematical model that considered how quickly various strains of HIV replicate, how fast they destroy cells and how immune systems respond to the virus.
They found that HIV progresses to AIDS when a "less-fit" variety of the virus succeeds over another strain, HealthDay News/Post reports. According to the researchers, that less-fit version then begins killing immune system cells extensively and rapidly while also restricting the number of times it replicates. The virus "basically kills its own habitat, its house," Wodarz said. He added that because this form of HIV is efficient at quickly killing large numbers of immune cells, "once these less-fit strains emerge, they can plunge the patient into AIDS."
According to Wodarz, two or more strains of the virus can co-infect the same immune cell, and if a fast-killing strain is among them, it will kill the cell before slower, but better-replicating forms can destroy the cell. "But without this ganging up on the same cell," HIV would "go extinct because evolution would select against it -- because it is less fit and replicates less," Wodarz said. Therefore, one method of delaying the progression of HIV to AIDS would be to allow one type of HIV to enter a cell at any given time, Wodarz said.
The study "throws into question a lot of the notions that have been accepted about the evolution" of the virus within a typical HIV-positive person, Wodarz said. Benigno Rodriguez, an assistant professor of medicine at Case Western Reserve University and a specialist in the evolution of HIV, said the study is an "interesting concept" but that it contains some flaws. According to Rodriguez, most available data show that HIV becomes more efficient at replicating as AIDS progresses. He also questioned the importance of several HIV strains infecting the same cell. "The data that we already have in hand shows that multiple infection is relatively infrequent," Rodriguez said. The scientists also did not consider that most AIDS patients' immune systems are not destroyed directly by the disease but by "bystander" mechanisms that accompany AIDS, according to Rodriguez. "In an individual with advanced disease, if you look at the number of cells that are actually infected [with HIV], we are talking less than 1%," Rodriguez said, adding, "But, in reality, that individual may have lost 20, 30, 50% of his immune cells." He also said the mathematical model should be tested outside laboratory settings. Wodarz said that experiment verification is needed, but he added that "mathematical models have led to great progress before" in HIV/AIDS research (Mundell, HealthDay News/Washington Post, 8/3).
An abstract of the study is available online.
Reprinted with permission from kaisernetwork.org. You can view the entire Kaiser Daily HIV/AIDS Report, search the archives, or sign up for email delivery at www.kaisernetwork.org/dailyreports/hiv. The Kaiser Daily HIV/AIDS Report is published for kaisernetwork.org, a free service of the Kaiser Family Foundation, by The Advisory Board Company. © 2007 by The Advisory Board Company and Kaiser Family Foundation. All rights reserved.