THE DOGMA: To treat the dense
resistance many long-term HIVers face, find three or more effective
meds. 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 go
for undetectable.
THE DOUBTER:
New York City’s Paul Bellman, MD, and other docs say we need more
calibrated strategies to control resistance and make each med last as
long as possible. He prescribes “dialing drugs up and down”—boosting
them in new ways, subtracting them, even sticking with meds that tests
show you’re already resistant to—and reducing immune activation
(production of the immune cells HIV uses to reproduce) to limit HIV’s
moving targets. Says Bellman, “Independent of viral load, patients with
higher immune activation progress faster, losing CD4 cells too
quickly.” 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) is
a popular and proven tactic: The Norvir monopolizes the liver enzymes
that process other PIs, forcing those PIs to linger—and work—longer.
Bellman’s leap is to play the same game with the nukes, adding low
doses of the cancer drug hydroxyurea (HU), whose enzyme-blocking power
gives the nukes added oomph. Bellman points out that when the first
entry inhibitor, Fuzeon, arrived, some patients quickly developed
resistance. Now he adds HU along with Fuzeon, and his HIVers keep on
responding.
DIALING DOWN:
As opposed to throwing mega-HAART at ’em, Bellman treats some long-term
HIVers with dense resistance by subtracting meds. That’s because
certain mutations apparently reduce immune activation, allowing HIVers
to hold on to CD4 cells. Resistance also sometimes seems to weaken the
virus, allowing you to keep, say, a partially effective nuke in the
lineup at a lower dose while sometimes removing the PI—along with its
side effects. Over time, Bellman says, some people can get by with
fewer—and less toxic—meds.
LOWERING THE VOLUME:
Bellman has found an immune activation “set point” that predicts
whether your HIV will quickly run amok—or just amble along with no
great ambitions. We don’t have any great drugs capable of lowering this
set point elegantly, but there are, along with HU, a handful of older
immune suppressors kicking around. Immune activation is a largely neglected corner of HIV research,
but fortunately, those digging there—including Bellman; Robert
Gallo, MD; and Steven Deeks, MD—are among our most creative and
courageous minds. They may yet find buried treasure.
