A 2005 HIV diagnosis hasn’t kept Houston’s Ellen Foots, 52, anight-shift postal clerk and grandmother of seven, from playingthree-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 ayear 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 adecade, because the triple punch seems best at keeping HIVundetectable. But Foots’ doctor, Joseph Gathe, MD, of Baylor College ofMedicine, invited her into his study of people taking only Kaletra—theprotease inhibitor (PI) lopinavir with a built-in booster of the PINorvir (ritonavir). At the low booster dose, Norvir doesn’t suppressHIV; thus lopinavir works on its own, making the regimen monotherapy.

Gathefirst began presenting surprising results in 2003, showing that thistherapy suppressed HIV in 21 patients—stabilizing or lifting CD4 countsas 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 maysuppress HIV on its own, hasn’t been studied as monotherapy.)

SomeHIV doctors aren’t betting the benefit will outweigh the risk. Indeed,monotherapy may be running into resistance of its own. One small studyrecently found that after 90 weeks, some on Kaletra alone developedresistance to PIs, while none on Kaletra plus two nukes did. ”It seemspretty clear that Kaletra monotherapy is not as effective as standardthree-drug therapy,” says Joel Gallant, MD, of Johns Hopkins School ofMedicine in Baltimore. New York City’s Howard Grossman, MD, formerdirector of the American Academy of HIV Medicine says, “I’m still veryhesitant about Kaletra monotherapy, although the results have beenbetter than I expected.”

Gathe says the recent study “hasn’tdampened my enthusiasm: The percentage of resistance in the mono arm isstill low and comparable to triple therapy studies with non-nukes.”Meanwhile, a small Spanish study echoed Gathe’s earlier monotherapyfindings: little resistance at 48 weeks.

The conflicting resultsare keeping the debate alive. Since Gathe’s original trial, severalothers—many funded by Abbott Laboratories, Kaletra’s manufacturer—haveproduced similar outcomes comparing monotherapy with three-drugregimens. In one, Kaletra monotherapy suppressed HIV as well as a comboof 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 athree-drug regimen—it’s not a replacement for triple therapy.” So whytry it at all? It’s all about the “real world” he says, “where we haveto compromise because of cost and [side effects].”

Replacing threedrugs with one to cut his patients’ copays, Gathe chose solo Kaletrabecause it mounts a fierce fight against HIV, with resistanceprevailing only after many missed doses. “For the individual, drugcosts drop by two thirds—and if they need the nuke, you can add it,”Gathe says. And eliminating nukes from combos may eliminate their sideeffects, such as fat loss and kidney and bone problems. Studies are nowexamining whether fat accumulation, often linked to PIs, occurs less ina nukeless PI regimen.

If monotherapy turns out to be safe for shortperiods of time but not in the long run, Gathe says, it could proveuseful  for people facing hep C treatment and needing an HIV regimenthat won’t promote anemia (some nukes do), or for those with resistanceto nukes and in need of a second combo. It’s also being studied for useduring pregnancy, he says.

Gathe’s “real world” approach has somesupport among HIV doctors. Boston’s Cal Cohen, MD, who has a fewpatients doing well on Kaletra monotherapy, says the studies show that“not everyone needs the second or third [HIV drug] to maintain viralsuppression—most don’t.” NYC’s Paul Bellman, MD, says he hopes thatconventional wisdom won’t obscure monotherapy’s “potentially importantplace in treatment both here and globally.”

Other prominent HIVdoctors say they wouldn’t prescribe the regimen in the U.S. “Why wouldyou?” asks Washington, DC’s, Douglas Ward, MD, adding that Kaletramonotherapy must be taken a demanding twice a day.

Advocate BobHuff of Treatment Action Group cites the studies in which monotherapydidn’t seem to keep people undetectable as consistently as three-drugcombos, meaning it might not prevent HIV drug resistance in the longterm. Grossman cautions that when such resistance does emerge, it maylimit use of other PIs. And NYC’s Lloyd Bailey, MD, says, “I don’tthink that sacrificing long-term success is currently worth theadvantage of reducing cost or avoiding the toxicity of [nukes].”

Asfor Foots, her viral load remains undetectable and her CD4 count atabout 800 after more than a year—with no side effects. She says she’llstick with monotherapy as long as this trend continues. She’s nothedging her bets.