| Literature DB >> 18625269 |
Masanori Kobayashi1, Koichiro Nakahara, Takahiro Seki, Shigeru Miki, Shinobu Kawauchi, Akemi Suyama, Chiaki Wakasa-Morimoto, Makoto Kodama, Takeshi Endoh, Eiichi Oosugi, Yoshihiro Matsushita, Hitoshi Murai, Toshio Fujishita, Tomokazu Yoshinaga, Edward Garvey, Scott Foster, Mark Underwood, Brian Johns, Akihiko Sato, Tamio Fujiwara.
Abstract
Resistance passage studies were conducted with five INIs (integrase inhibitors) that have been tested in clinical trials to date: a new naphthyridinone-type INI S/GSK-364735, raltegravir, elvitegravir, L-870,810 and S-1360. In establishing the passage system and starting from concentrations several fold above the EC(50) value, resistance mutations against S-1360 and related diketoacid-type compounds could be isolated from infected MT-2 cell cultures from day 14 to 28. Q148R and F121Y were the two main pathways of resistance to S/GSK-364735. Q148R/K and N155H, which were found in patients failing raltegravir treatment in Phase IIb studies, were observed during passage with raltegravir with this method. The fold resistance of 40 mutant molecular clones versus wild type virus was compared with these five INIs. The overall resistance pattern of S/GSK-364735 was similar to that of raltegravir and other INIs. However, different fold resistances of particular mutations were noted among different INIs, reflecting a potential to develop INIs with distinctly different resistant profiles.Entities:
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Year: 2008 PMID： 18625269 DOI： 10.1016/j.antiviral.2008.06.012
Source DB: PubMed Journal: Antiviral Res ISSN： 0166-3542 Impact factor: 5.970