The Body Covers: The 6th Conference on Retroviruses and Opportunistic Infections
Abstract No. 603: Resistance Profile and Drug Combination Studies of an HIV-1 Protease Inhibitor BMS-232632
February 3, 1999
This presentation by Gong and colleagues at Bristol-Myers Squibb provides in vitro data of a new protease inhibitor in development that promises desirable features of once daily dosing, good tolerability and a resistance profile that appears (at this time) to differ markedly from the existing group of protease inhibitors.Abstract: Resistance Profile and Drug Combination Studies of an HIV-1 Protease Inhibitor BMS-232632
An azapeptide, this protease inhibitor exhibits EC50 values well below the currently licensed group of protease inhibitors, with values of 2-5 nM., which is also well below the concentration of drug that induces cellular toxicity (CC50=2850 microM). Serial passage of virus in the presence of drug (to induce resistance mutations) demonstrated a delayed appearance of mutations (relative to saquinavir and ritonavir) and then the appearance of a different mutation N88S upon genotypic analysis. Cross resistance studies involving 5 other protease inhibitors indicated that BMS-232632 resistant virus remained sensitive to saquinavir while showing some resistance to nelfinavir, ritonavir, indinavir and amprenavir. In reciprocal cross resistance studies testing the sensitivity to BMS-232632 of strains resistant to nelfinavir, saquinavir and amprenavir, these viruses demonstrated sensitivity to the drug, while indinavir and ritonavir resistant virus displayed partial cross-resistance to BMS-232632.
Authored by: Y. Gong, B. Robinson, R. Rose, K. Riccardi, C. Deminie, D. Stock, T. Spicer, F. Djang, J. Cross, R. Colonno, and P.F. Lin
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