A 2005 HIV diagnosis hasn’t kept Houston’s Ellen Foots, 52, a
night-shift postal clerk and grandmother of seven, from playing
three-card poker and slots. She’s no slouch at keno, either: Recently,
with only $125 of chips left, she won $800. “I bought some clothes,
paid the bills and gave my children some money,” says Foots.
About a
year ago, when her lab reports said it was time to start HIV meds,
Foots took another gamble. A three-drug combo has been the norm for a
decade, because the triple punch seems best at keeping HIV
undetectable. But Foots’ doctor, Joseph Gathe, MD, of Baylor College of
Medicine, invited her into his study of people taking only Kaletra—the
protease inhibitor (PI) lopinavir with a built-in booster of the PI
Norvir (ritonavir). At the low booster dose, Norvir doesn’t suppress
HIV; thus lopinavir works on its own, making the regimen monotherapy.
Gathe
first began presenting surprising results in 2003, showing that this
therapy suppressed HIV in 21 patients—stabilizing or lifting CD4 counts
as well. A year later, it was still working in all 21. Now, he says,
“We’re dead in the middle of these studies—and designing new ones”
to evaluate the risk-benefit ratio. (Norvir-boosted Reyataz, which may
suppress HIV on its own, hasn’t been studied as monotherapy.)
Some
HIV doctors aren’t betting the benefit will outweigh the risk. Indeed,
monotherapy may be running into resistance of its own. One small study
recently found that after 90 weeks, some on Kaletra alone developed
resistance to PIs, while none on Kaletra plus two nukes did. ”It seems
pretty clear that Kaletra monotherapy is not as effective as standard
three-drug therapy,” says Joel Gallant, MD, of Johns Hopkins School of
Medicine in Baltimore. New York City’s Howard Grossman, MD, former
director of the American Academy of HIV Medicine says, “I’m still very
hesitant about Kaletra monotherapy, although the results have been
better than I expected.”
Gathe says the recent study “hasn’t
dampened my enthusiasm: The percentage of resistance in the mono arm is
still low and comparable to triple therapy studies with non-nukes.”
Meanwhile, a small Spanish study echoed Gathe’s earlier monotherapy
findings: little resistance at 48 weeks.
The conflicting results
are keeping the debate alive. Since Gathe’s original trial, several
others—many funded by Abbott Laboratories, Kaletra’s manufacturer—have
produced similar outcomes comparing monotherapy with three-drug
regimens. In one, Kaletra monotherapy suppressed HIV as well as a combo
of non-nuke Sustiva (efavirenz) plus two-nukes-in-one Combivir
(AZT/3TC)—with less fat loss (lipoatrophy).
In the long term,
Gathe says, “I don’t think you’ll see Kaletra mono winning against a
three-drug regimen—it’s not a replacement for triple therapy.” So why
try it at all? It’s all about the “real world” he says, “where we have
to compromise because of cost and [side effects].”
Replacing three
drugs with one to cut his patients’ copays, Gathe chose solo Kaletra
because it mounts a fierce fight against HIV, with resistance
prevailing only after many missed doses. “For the individual, drug
costs drop by two thirds—and if they need the nuke, you can add it,”
Gathe says. And eliminating nukes from combos may eliminate their side
effects, such as fat loss and kidney and bone problems. Studies are now
examining whether fat accumulation, often linked to PIs, occurs less in
a nukeless PI regimen.
If monotherapy turns out to be safe for short
periods of time but not in the long run, Gathe says, it could prove
useful for people facing hep C treatment and needing an HIV regimen
that won’t promote anemia (some nukes do), or for those with resistance
to nukes and in need of a second combo. It’s also being studied for use
during pregnancy, he says.
Gathe’s “real world” approach has some
support among HIV doctors. Boston’s Cal Cohen, MD, who has a few
patients doing well on Kaletra monotherapy, says the studies show that
“not everyone needs the second or third [HIV drug] to maintain viral
suppression—most don’t.” NYC’s Paul Bellman, MD, says he hopes that
conventional wisdom won’t obscure monotherapy’s “potentially important
place in treatment both here and globally.”
Other prominent HIV
doctors say they wouldn’t prescribe the regimen in the U.S. “Why would
you?” asks Washington, DC’s, Douglas Ward, MD, adding that Kaletra
monotherapy must be taken a demanding twice a day.
Advocate Bob
Huff of Treatment Action Group cites the studies in which monotherapy
didn’t seem to keep people undetectable as consistently as three-drug
combos, meaning it might not prevent HIV drug resistance in the long
term. Grossman cautions that when such resistance does emerge, it may
limit use of other PIs. And NYC’s Lloyd Bailey, MD, says, “I don’t
think that sacrificing long-term success is currently worth the
advantage of reducing cost or avoiding the toxicity of [nukes].”
As
for Foots, her viral load remains undetectable and her CD4 count at
about 800 after more than a year—with no side effects. She says she’ll
stick with monotherapy as long as this trend continues. She’s not
hedging her bets.
