Conference on Retroviruses and Opportunistic Infections

There were no T cell-jolting developments, but new ground was broken at the prestigious eighth-annual Conference on Retroviruses and Opportunistic Infections in Chicago in February. Tongues were wagging about antiretrovirals -- good results with new classes, including fusion inhibitors and chemokine attackers, and with side-effect reduction -- a new Bristol Myers protease inhibitor (BMS-232632) is potent but doesn't raise blood fats. POZ will keep you posted, as these advances develop (or not) into solutions for lipodystrophy and drug resistance. Meanwhile, eyeball the hot type below.

THE BUZZ	THE DATA	THE CATCH
1. DRUG HOLIDAYS
The biggest news was that HIVers may be able to do less time on antiretroviral therapy. Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, reported promising data about the seven-days-on, seven-days-off med cycle called structured intermittent therapy (SIT). Most doctors have been, at best, cautious about this experiment, fearing that on-offing might quicken viral resistance and drug failure. But it didn't happen here, leading to hope that SIT approaches might provide important advantages: lower overall med costs, fewer side effects and blessed breaks from a punishing pill regimen.	In Chicago, Fauci updated his small SIT study that has grabbed big headlines. Having first reported last year positive findings for five HIVers on cycles, he now presented data for 10 HIVers, none of whom has completed more than 22 on-off cycles (44 weeks). But so far, Fauci says, the results look good. "It's a big deal to patients if you don't have to take drugs 50 percent of the time. The virus doesn't rebound. There is no negative impact on the immune system and no emergence of resistance." Also, he notes, adherence has been good, but he insisted that no one should try this at home until there's more data.	SIT is done only with HAART drugs that leave the bloodstream quickly; not all antiretrovirals do. A slow decline in drug levels when the medication is stopped could raise the chance that HIV meets up with a suboptimal amount of drug in the blood, boosting the virus' odds of mutating and becoming resistant to that med. For that reason, researchers warn that efavirenz (Sustiva) and abacavir (Ziagen) are SIT no-nos; similarly, with regimens containing low-dose ritonavir to slow the breakdown of other protease inhibitors, the ritonavir must be stopped a day before the other drugs.
2. LIQUID KALETRA
It may not be a triple-dip double chocolate cone with jimmies, but Abbott's new lopinavir/ritonavir (Kaletra) liquid is that rare treat: a protease inhibitor (PI) that kids are willing to swallow. The icky taste of the first PI liquids made them a no-go for many kids, but studies have shown they like Kaletra better. It's effective and it is the only PI approved for children as young as 6 months. This is terrific news because not only do most kids now have a PI option, but this better-tasting version reduces the chances that they might be downing inadequate amounts or skipping doses. These errors increase the odds of resistance -- bad news when the pediatric pipeline is more desert than dessert.	In a study of 100 children (ages 6 months to 12 years), Kaletra was generally well-tolerated -- only 2 percent stopped taking the drug. Effectiveness of the drug continued to look good at 48 weeks, with 84 percent (37 out of 44 kids) who had never before ridden the roller-coaster of combo therapy still with undetectable viral loads on Kaletra plus the nukes d4T (Zerit) and 3TC (Epivir). Children who were treatment veterans used a different regimen: Kaletra plus nevirapine (Viramune) plus one or two nukes. In those who had previously taken only nukes, 88 percent maintained undetectable viral levels.	Children who had previously taken both PIs and nukes (but had never tried the non-nukes) were generally not so lucky -- although the virus remained undetectable in 58 percent (14 of 24 kids at 48 weeks). Adverse effects were few: Three children developed hypercholesterolemia (cholesterol excess in the blood) and one child had hypertriglyceridemia (triglycerides excess in the blood) -- both woes are also very common among grownup PI-takers. Two unlucky kids discontinued Kaletra by week 60; one because of pancreatitis and another because of Burkitt's lymphoma, both of which were thought to be related to Kaletra.
3. ANTI-RESISTANCE DRUGS
Belgian firm Tibotec is trumpeting its newest salvage-therapy coup: the development of what Tibotec calls "resistance repellent" drugs in both the PI and non-nuke classes. If these meds pass muster, the 30 to 40 percent of HAART-takers already resistant to various antiretrovirals can heave a big sigh of relief. But those in need of salvage therapy won't be the only fans. Tibotec's agents are designed not only to fight resistant virus but to actually stop resistance-creating HIV mutations; best case scenario: Monotherapy might one day be an option.	Tibotec's non-nuke, TMC-120, was shown to be potent when treatment-naive HIVers taking the drug as monotherapy (50 mg or 100 mg, twice daily) had significant viral-load decreases (on average, a 1.5 log drop). Although Tibotec has only test-tube results for its PI, TMC-126, the data look impressive: 95 percent of multidrug-resistant HIV was fully susceptible to it.	As with most anti-HIV drugs dribbling down the pipeline, much more research is needed before promises turn into practice and lives are saved. The proof will be in the pudding: Do Tibotec's anti-resistance TMCs block the return of the mutant monster in everyone, especially those who need them most: HAART vets at the end of their treatment hopes? The Belgian firm plans to begin trials in Europe this year. Hope for good results, because with each passing day, more and more HIVers join the salvage-therapy crowd. [Go to top]