Magazine article Drug Topics

New Protease Inhibitor Offers Favorable Resistance Pattern

Magazine article Drug Topics

New Protease Inhibitor Offers Favorable Resistance Pattern

Article excerpt

A new protease inhibitor, granted accelerated approval for use in combination with other antiretrovirals for the treatment of HIV, arrives with several promising features.

Like most protease inhibitors, Agenerase (amprenavir, Glaxo Wellcome) appears to possess considerable activity against HIV-1. A 24week analysis of two well-controlled studies indicated that the drug, when used in triple-combo therapy, achieved viral loads of less than 400 copies/ml in previously untreated HIV patients, as well as in those who received prior antiretroviral therapy Amprenavir's rather favorable differentiating factor from other protease inhibitors appears to be its resi tance pattern. The key mutation assodated with resistance to amprenavir was identified at codon 50 of the HIV1 protease substrate binding site. This critical mutation was not observed in protease inhibitor therapy-experienced patients or as a naturally occurring variant in persons living with HIV. Based on these findings, Glaxo Wellcome has suggested that amprenavir may potentially be used as an alternative for HIV patients who have developed resistance to currently available protease inhibitors.

That prospect, however, requires further evaluation since labeling states that the actual I potential for protease inhibitor crossresistance in HIV isolates from amprenavir-treated patients has not been fully evaluated.

Another favorable characteristic amprenavir brings is a relatively convenient dosing schedule. "There is a great need for dosing flexibility with antiretroviral therapy; amprenavir has a long half-life and can be dosed twice a day," noted Jeff Goodgame, M.D., principal investigator, Central Florida Research Initiative. As a resuit, "this drug may help simplify combination therapy by offering less restrictive dosing patterns," he said.

The most frequently reported adverse effects were nausea, diarrhea, vomiting, rash, and perioral paresthesia. Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, have occurred in 1% of patients treated with amprenavir As with other protease inhibitors, amprenavir may be associated with acute hemolytic anemia, diabetes mellitus, and hyperglycemia.

Since their momentous introduction, protease inhibitors have made quite an impact on HIV patients' quality of life. In reflecting on the advances in HIV treatment this potent antiretroviral class is responsible for, Samuel Uretsky, Pharm. …

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