HIV is a frustrating foe, but at least doctors have been able to count on a few solid principles to help them fight the virus. Now, a group of scientists calling itself 'The Bad Boys of Cleveland' reports evidence that rebels against one of those principles. The findings cement a feeling that has been growing in the HIV research community: that the virus enlists patients' own defences to dismantle their immune systems.

This revises the picture first painted a decade ago, when studies reported that levels of HIV in a patient's blood predict how fast the patient will lose vital T cells. Since then, doctors have believed that the virus is the main trigger for T-cell loss. They rely on measurements of viral load to help them decide when and how to treat patients with HIV.

But it is increasingly clear that virus levels are only a small part of the story. In fact, as Benigno Rodriguez of Case Western Reserve University in Cleveland reports this week, viral load explains only 4–6% of the rate at which a patient's T cells disappear (B. Rodriguez et al. J. Am. Med. Assoc. 296, 1498–1506; 2006).

Rodriguez and his collaborators in California, Massachusetts and Washington examined blood samples from thousands of patients dating from 1984. They analysed the patients' viral load and T-cell count before treatment with antiretroviral drugs. The group found that, in general, patients with higher viral loads lost their T cells faster than those with lower virus levels. But the disease progressed at different rates in patients with similar viral loads. This suggests that something other than virus levels alone is driving T-cell loss.

Now, scientists must find out what that is. Many suspect that a phenomenon called immune activation is an important factor. This is the idea that HIV whips the body's immune system into a frenzy, and that this flurry of activity eventually triggers T-cell death. “This paper will help shift the focus of basic research to immune activation,” says immunologist Zvi Grossman of the US National Institutes of Health in Bethesda, Maryland.

The paper is also a score for the Bad Boys — a group of immunologists who have been meeting informally over the past two years. They include about 30 scientists, including Grossman, of whom a handful are 'Bad Girls'.

A T cell (green) infected with HIV (pink), which is budding away from the cell membrane. Credit: NIBSC/SPL

We've been doing this on a shoestring — people pay their own air fare. They come because they like the atmosphere.

The Bad Boys were first convened by Michael Lederman, head of the Case Western Reserve University Center for AIDS Research and senior author of the recent paper. “The idea was to have a relaxed but intense forum where we could present our unpublished data, share ideas, then go back to our lives and work some more,” Lederman says. “We've been doing this on a shoestring — people pay their own air fare. They come because they like the atmosphere in which we work.”

Many see that informal approach as a more refreshing form of collaboration than the large, top-down structures fashionable in HIV research these days (see Nature 442, 610–611; 2006). But in their fight against orthodoxy, the Bad Boys have made one concession to scientific propriety. The Journal of the American Medical Association paper is the first to reference the Bad Boys, but it acknowledges the group by a much blander name: the Cleveland Immunopathogenesis Consortium. Lederman admits that the wordy title “lacks panache” compared with the Bad Boys nickname. But, he says: “We were anxious that editors might give us grief.”