Triple nuke nightmare.

Last July, an Important Drug Warning was issued to healthcare providers concerning a high rate of virologic failure with a once-daily, 3-drug combination of Viread, Epivir, and Ziagen. Data from study ESS30009, which compared Sustiva versus Viread in combination with once-daily Ziagen/Epivir,

revealed poor performance in patients taking Viread plus Ziagen/Epivir arm. Data from a pilot study presented at the 2nd IAS Conference in Paris also indicated a high rate of failure (inability to lower viral load and to keep it undetectable) with this combination. The warning recommended that this combination not be used in HIV+ patients and that patients experiencing good control of virus on this therapy should be closely monitored. Changing or strengthening treatment should be considered in these patients. The warning also recommended close monitoring of patients using this triple-drug combination with any other HIV drugs. Because the combination of Viread and Epivir has been widely used already, the problem is likely between Viread and Ziagen. Researchers from Gilead (maker of Viread) and GlaxoSmithKline (maker of Epivir and Ziagen) are working to try to determine the reason behind this "perfect storm" of a bad HIV regimen. In addition, at the time this issue of HIV Treatment ALERTS! went to press, a "Dear Healthcare Professional" letter was issued by Gilead warning about the once-daily combination of Viread, Videx, and Epivir.

BOTTOM LINE: Avoid therapy that is made up of all nucleoside reverse transcriptase inhibitors ("nukes"). The one possible exception right now is Retrovir, Epivir, and Ziagen (available in one pill as Trizivir), but even this combination is considered weaker than other options using non-nukes or protease inhibitors (see "Bottom Lines" in May 2003 issue of HIV Treatment ALERTS!) If you are taking a triple-nuke HIV regimen, talk to your doctor immediately about the possibility of switching to another combination--even if the current combination is working for you.