AIDS abated; genome scans illuminate immune control of HIV.

Some people who contract HIV, the virus that causes AIDS, maintain low amounts of the virus in their bodies for years. These long-term nonprogressors--so called because a decade or more can pass before they develop full-blown AIDS--have attracted great attention from researchers.

Now, using powerful, whole-genome scans, researchers have identified three genetic variations that partially explain why some HIV-infected people develop AIDS quickly while others keep it at bay.

"This is a good head start to unraveling the genetic basis of good control of viral load," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., which funded the study. Study leader David Goldstein of Duke University in Durham, N.C., says that the ultimate goal is to develop drugs or vaccines that boost the immune system's ability to fight HIV.

Upon HIV infection, the amount of virus spikes, after which the immune system establishes a detente that keeps the virus count in the blood steady. However, this viral set point, as it's called, varies tremendously from person to person. Some people maintain an undetectable amount of virus, while others carry millions of copies in each drop of blood.

To understand this variability, a large, multinational team reviewed the files of 30,000 HIV-positive patients and selected 486 with well-documented viral counts. Blood from each patient was analyzed with a genome chip--a small glass or plastic slide that detects variations at 550,000 specific points in the human genome. Such chips, which only recently became available, can quickly identify genes associated with disease (SN: 6/9/07, p. 355).

In this case, the scans pinpointed the three genetic variations that most strongly predicted a low viral count or a slow progression to AIDS, according to a report published online July 19 by Science.

One protective variation was in a gene called HCP5. Goldstein says that the gene presents an intriguing subject for further study because it is an endogenous human retrovirus. That is, HCP5 is a genetic fossil of an ancient virus that once infected people and eventually wormed its way into the human genome. "We're working hard to establish if this new gene contributes to [HIV] control," says Goldstein.

The HCP5 variation frequently occurs in conjunction with a particular version of an immune system gene called HLA-B. Earlier work with long-term nonprogressors also pointed to this gene as important in keeping HIV in check. "Right away, this [new finding about HLA-B] validates the methodology," says Fauci, who notes that the study is the first to use whole-genome chips in HIV research.

The second highlighted variation points to a closely related gene, HLA-C. This gene hadn't before been implicated in HIV control, says Goldstein. "It's possible that a vaccine that [boosts] HLA-C may hit a vulnerable point for HIV," he says.

The team found a third genetic variation in a genome region near two genes that are now being studied intensively but aren't involved in the immune system.

Together, the three genetic variations account for about 15 percent of the variability in people's viral set points, the researchers say. With a larger group of patients, Goldstein "strongly suspects" that the team will soon find other genes that contribute to immune control of HIV.

STATS

1 in 300

Proportion of HIV-infected people with undetectable amounts of virus