The most common side effects seen in the Phase 3 DUET studies were rash (17%), diarrhea (15%), nausea (14%), and headache (9%). The rashes seen with etravirine were generally mild to moderate and resolved with continued dosing.
Potential drug interactions:
Intelence should not be used with unboosted (without Norvir) PIs (Intelence lowers their levels), Aptivus (Intelence level is lowered 76% with Aptivus), or with Sustiva, Viramune or full-dose (600 mg twice daily) Norvir (Intelence levels are lowered with each of these). Intelence has been studied and can be used without dose adjustment with the boosted protease inhibitors Prezista/Norvir and Invirase/Norvir. Cannot be taken with Reyataz/Norvir, Lexiva/Norvir, or Aptivus/Norvir. Kaletra increases Intelence blood levels, use together with caution. Intelence may be given without dose adjustment with Isentress and the experimental integrase inhibitor elvitegravir, but does require dose adjustment with Selzentry (600 mg twice daily Selzentry). In people with failed therapy with other non-nukes, Intelence should not be taken only with nukes (including Viread). No interaction was found with the acid suppressants ranitidine (Zantac and others) or Prilosec (omeprazole) when given with Intelence. There was also no interaction with methadone and Intelence.
Tips:
Received accelerated approval by the FDA as Positively Aware went to press. (Was not yet approved when pull-out chart was printed.) Intelence is a badly needed drug in the non-nuke class. The current non-nukes can develop resistance quickly, and with only one mutation in the virus. The second-generation Intelence was developed to have a higher genetic barrier to drug resistance. It has shown significant viral load reduction in people with drug resistance to Sustiva or Viramune, although it may work better for Sustiva failure (people with the HIV mutation K103N). Sustiva and Viramune are known for potency and tolerability compared to the protease inhibitors, although they have the potential for very negative side effects. Remember also that Sustiva should not be taken during pregnancy and that Viramune may lead to liver damage or life-threatening rash. Intelence is likewise generally tolerable. Diarrhea is a commonly reported side effect in studies, but the incidence is not much higher than the comparative arms. Intelence showed a nearly 2 log drop in viral load (99% reduction in circulating virus) in a 7-day monotherapy study with people taking HIV meds for the first time, evidence of tremendous potency. Benefits in this group, however, have not been established. In another early study in people with NNRTI resistance, Intelence substituted for 7 days for the failing NNRTI led to about a 1 log drop (90% reduction) in viral load. One Phase 2 study was stopped, however, when Intelence didn't perform as well as the protease inhibitors in the comparator group of people, but in this study Intelence was not given with other active drugs in the regimen. In a Phase 2b study presented at the 2006 International AIDS Society meeting, 199 individuals with documented NNRTI resistance were randomized to receive either Intelence or another type of drug regimen (a comparator). The viral load reduction in people receiving an Intelence regimen was significantly greater than in the comparator group with optimized therapy. The DUET studies recently published demonstrated good activity when combined with Prezista in treatment-experienced people. In the recent Phase 3 DUET studies in treatment-experienced individuals with NNRTI resistance, a significantly greater number (59%) treated with Intelence than placebo (41%) reached an undetectable (less than 50 copies) viral load. These are encouraging results. It is important to remember that as the clinical studies are being completed, we will find out more information about this new drug. Tibotec is also developing another non-nuke, TMC-278, which may have pharmacologic advantages over 125, including the ability to dose once a day.
Doctor
Etravirine was available through an early access program (EAP), and was approved early in 2008. It's a "second generation NNRTI," which means that it can work when other NNRTIs have failed. The DUET studies showed that etravirine was more effective than placebo (in combination with other drugs) in people with resistance to other drugs, including NNRTIs. However, if you have lots of NNRTI mutations (and specifically three or more etravirine mutations), it won't be as effective. That's why it's important not to keep taking Sustiva or Viramune if they're not working, because you'll continue to collect drug mutations that could lead to cross-resistance to etravirine. -- Joel Gallant, M.D.
Activist
Intelence is a new player in the non-nucleoside class. It received FDA approval in January of 2008. It offers one major advantage over other drugs in this class -- it can still work after resistance develops to any of the others. In short, Intelence restores the use of this class for people who had previously developed resistance to it. Intelence has a good side effect profile, showing only a small amount of rash, diarrhea, and headache. While it has been primarily tested by the manufacturer, Tibotec Therapeutics, in people who had prior resistance to Sustiva or Viramune, there is no reason not to expect it to perform well as first or second line therapy. It is not a once-a-day drug, which some consider a competitive disadvantage relative to Sustiva, but once daily dosing may be an overrated benefit. Few people with HIV actually take drugs only once a day, even if their primary HIV regimen is a once-daily drug. Tibotec has a second drug of this type well along in clinical studies. -- Martin Delaney
