THE DOGMA: To treat the denseresistance many long-term HIVers face, find three or more effectivemeds. Never start a new combo with fewer than two. If all else fails,try the kitchen sink—a six-plus combo, a.k.a mega-HAART. And always gofor undetectable.

THE DOUBTER:New York City’s Paul Bellman, MD, and other docs say we need morecalibrated strategies to control resistance and make each med last aslong as possible. He prescribes “dialing drugs up and down”—boostingthem in new ways, subtracting them, even sticking with meds that testsshow you’re already resistant to—and reducing immune activation(production of the immune cells HIV uses to reproduce) to limit HIV’smoving targets. Says Bellman, “Independent of viral load, patients withhigher immune activation progress faster, losing CD4 cells tooquickly.” You may want to tune your doctor into his dogma-defying methods, including:

DIALING UP:Using small doses of Norvir to boost other protease inhibitors (PIs) isa popular and proven tactic: The Norvir monopolizes the liver enzymesthat process other PIs, forcing those PIs to linger—and work—longer.Bellman’s leap is to play the same game with the nukes, adding lowdoses of the cancer drug hydroxyurea (HU), whose enzyme-blocking powergives the nukes added oomph. Bellman points out that when the firstentry inhibitor, Fuzeon, arrived, some patients quickly developedresistance. Now he adds HU along with Fuzeon, and his HIVers keep onresponding.

DIALING DOWN:As opposed to throwing mega-HAART at ’em, Bellman treats some long-termHIVers  with dense resistance by subtracting meds. That’s becausecertain mutations apparently reduce immune activation, allowing HIVersto hold on to CD4 cells. Resistance also sometimes seems to weaken thevirus, allowing you to keep, say, a partially effective nuke in thelineup at a lower dose while sometimes removing the PI—along with itsside effects. Over time, Bellman says, some people can get by withfewer—and less toxic—meds.

LOWERING THE VOLUME:Bellman has found an immune activation “set point” that predictswhether your HIV will quickly run amok—or just amble along with nogreat ambitions. We don’t have any great drugs capable of lowering thisset point elegantly, but there are, along with HU, a handful of olderimmune suppressors kicking around. Immune activation is a largely neglected corner of HIV research,but fortunately, those digging there—including Bellman; RobertGallo, MD; and Steven Deeks, MD—are among our most creative andcourageous minds. They may yet find buried treasure.