Teams expose HIV's first lethal strike
Mounting evidence of early immune damage argues for change in treatments.
HIV, the virus that causes AIDS, slaughters swathes of vulnerable immune cells from the moment it enters the body, two studies show. The findings are helping to fuel a rethink of strategies to predict patients' prospects and to design vaccines and drugs.
Doctors long thought that HIV takes years to inflict real damage on the body, partly because patients can lack symptoms for a decade or more. But researchers have begun to suspect that the virus wreaks havoc within the first few days.
Now two research groups have examined the extent of immediate harm inflicted by HIV, and investigated how the virus does it. They did this by studying monkeys in the days after they were infected with SIV, a virus similar to HIV, and they publish their results online in Nature1,2.
Within a few days of infection, SIV infects up to 60% of a particular type of immune cell, called memory CD4+ cells, and it goes on to kill about half of them, report Mario Roederer and his team at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. These cells are responsible for remembering infectious agents and triggering the immune system to attack them.
The findings add to mounting evidence that the onslaught of HIV is much fiercer than doctors once thought. These cells "are the combat soldiers of the immune system, and they are wiped out", says immunologist Louis Picker, who studies the virus at Oregon Health and Science University in Portland.
Roederer's team also examined how the virus eradicates these cells so effectively, something that HIV scientists have been debating. He believes that the virus worms its way into all of the cells it kills. But in the other study, Ashley Haase of the University of Minnesota in Minneapolis and his colleagues argue that the virus also triggers cell suicide in many cells without actually invading them.
The idea that HIV inflicts severe damage very early in infection stemmed from a 1998 paper showing that SIV quickly obliterates CD4+ cells in the guts of monkeys3. Researchers say that the wider medical community is only now beginning to catch on.
The discovery is prompting a shift in the way scientists think about the course and treatment of the infection. It suggests, for example, that the slow crumbling of patients' immune systems, and their increased vulnerability to infection, is triggered by the early viral damage. "You have a massive wound in the first three months of infection and the patient dies slowly as a result," Picker says.
If this is true, then the number of immune cells killed by HIV in its first few days might be used to predict how quickly the disease will advance in a particular patient.
The realization could also prompt changes in the way experimental vaccines are devised and tested. It suggests that a jab must stop the infection at its earliest stages: perhaps by working in the gut, where the destruction of immune cells is most dramatic. "You've got to have something that works at the portal of entry," Haase says.
The results also back the case for giving drugs as a preventative measure to groups at very high risk of infection, such as sex workers, to prevent the virus gaining a foothold. And researchers may need to find ways of supplementing existing antiviral drugs with treatments that regenerate the devastated population of memory CD4+ cells, Picker suggests.
- Mattapallil J. J., et al. Nature, advance online publication doi: 10.1038/nature03501 (2005).
- Li Q., et al. Nature, advance online publication doi: 10.1038/nature03513 (2005 ).
- Veazey R. S., et al. Science, 280. 427 - 431 (1998).
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