Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants
| Autor: | Hitoshi Murai, Tamio Fujiwara, Makoto Kodama, Chiaki Wakasa-Morimoto, Mark R. Underwood, Shigeru Miki, Scott A. Foster, Toshio Fujishita, Edward P. Garvey, Brian A. Johns, Yoshihiro Matsushita, Masanori Kobayashi, Koichiro Nakahara, Akihiko Sato, Takeshi Endoh, Tomokazu Yoshinaga, Eiichi Oosugi, Takahiro Seki, Akemi Suyama, Shinobu Kawauchi |
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| Rok vydání: | 2008 |
| Předmět: |
T-Lymphocytes
Mutant Drug Evaluation Preclinical Integrase inhibitor HIV Infections HIV Integrase Biology medicine.disease_cause Virus Cell Line Virology Drug Resistance Viral medicine Humans HIV Integrase Inhibitors Pharmacology Mutation Elvitegravir Raltegravir biology.organism_classification Cell culture Lentivirus HIV-1 HeLa Cells medicine.drug |
| Zdroj: | Antiviral Research. 80:213-222 |
| ISSN: | 0166-3542 |
| DOI: | 10.1016/j.antiviral.2008.06.012 |
| Popis: | 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 EC50 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. |
| Databáze: | OpenAIRE |
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