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  • Title: Protease inhibitors: resistance, resistance, resistance.
    Author: Gilden D, Falkenberg J, Torres G.
    Journal: GMHC Treat Issues; 1997 Feb; 11(2):5-10. PubMed ID: 11364108.
    Abstract:
    Current anti-HIV drugs are plagued by problems with development of resistance. Reports at the 4th Annual Conference on Retroviruses and Opportunistic Infections proposed various ways to use protease inhibitor-containing combinations to build a high enough genetic barrier against HIV breakthrough. Two studies confirmed that potent highly active antiretroviral therapy combination therapies can be beneficial even to people with advanced AIDS and with extensive past exposure to anti-HIV therapy. While nelfinavir has shown itself to be a respectable protease inhibitor, optimum dosage questions still persist and the issue of cross-resistance is a concern. Abbott laboratories revealed its new protease inhibitor ABT-378. ABT-378 is highly active against HIV, even more so than ritonavir. Toxicity information about ABT-378 or what drug levels to use to avoid resistance are not known. Two studies that achieved some success in HIV treatment by combining protease inhibitors are also reported. Currently, there are 12 possible double protease inhibitor combinations using the three protease inhibitors on the market and nelfinavir. However, while ritonavir works with saquinavir and possibly ABT-378, there may be interference between protease inhibitors because they compete for the same binding sites on HIV protease, thus weakening the overall effect to less than the sum of their individual effects.
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