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HIV can be deadly even before CD4 counts fall, researchers say

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An infection by the virus that causes AIDS can increase risk of premature death even before the immune system has deteriorated to the point where most physicians begin antiviral therapy, British researchers said Thursday.

An infection by the virus that causes AIDS can increase risk of premature death even before the immune system has deteriorated to the point where most physicians begin antiviral therapy, British researchers reported Thursday. The finding suggests that treatment should start even earlier than it is now and supports the current plans of world bodies to begin treating HIV infections in the developing world earlier.

The most common marker of an HIV infection is the level of an immune cell called CD4 that is the target of the virus. In a healthy individual, CD4 levels are generally over 500 cells per cubic millimeter and can go as high as 1,500. A level below 200 sharply increases the risk of the infections and other illnesses that are the markers for full-blown AIDS. Most physicians in the industrial world now begin treatment when a patient’s CD4 levels fall below 350. In the developing world — at least in part because of the shortage of resources — treatment has generally begun when the level falls to 200, but UNAIDS announced last week that it would now begin treatment at 350.

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Epidemiologist Rebecca Lodwick of the University College London Medical School and her colleagues analyzed data from 23 North American and European cohorts of HIV-positive individuals between the ages of 20 and 29. They reported in the journal Lancet that, when they accounted for other factors affecting deaths, homosexual men with counts between 350 and 500 and who had not received antiviral therapy were 30% more likely than uninfected individuals to die. Heterosexuals were nearly three times as likely to die, injection drug users were more than nine times as likely to die, and those with unknown risk factors were four and one-half times as likely to die.

“The increase in risk was substantial in injecting drug users and the heterosexual group, but was small in men who have sex with men,” the authors said in a statement. “This finding suggests that much of the raised risk in the former two risk groups probably results from confounding by socioeconomic and lifestyle factors rather than being an effect of HIV infection itself. The magnitude of the raised risk in the [homosexual] group is more likely to reflect the effect of HIV itself.”

Whether starting therapy even earlier than is now done would reduce this increased risk is not known, researchers from the Harvard Medical School wrote in an editorial in the same journal. A clinical trial to test this possibility is now underway, but results are not expected for several years. Meanwhile, they said, physicians should aggressively screen for, prevent and treat risk factors that might contribute to the increased risk.

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