Cross-Resistance Profile Determination of Two Second-Generation HIV-1 Integrase Inhibitors Using a Panel of Recombinant Viruses Derived from Raltegravir-Treated Clinical Isolates ▿
| Autor: | C. Cleybergh, H. De Wolf, Ann Verheyen, Lieven Jozef Stuyver, Evelien Rondelez, L. Van Wesenbeeck, K Van Baelen, Veerle Smits, K. Van der Borght, Maxim Feyaerts |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Pharmacology
Elvitegravir Integrase inhibitor Biology Quinolones Raltegravir Recombinant virus biology.organism_classification Virology Antiviral Agents Virus Pyrrolidinones Integrase Infectious Diseases Raltegravir Potassium Lentivirus medicine biology.protein HIV-1 Humans Pharmacology (medical) HIV Integrase Inhibitors Cross-resistance medicine.drug |
| Popis: | The integrase inhibitor raltegravir (RAL) is currently used for the treatment of both treatment-naïve and treatment-experienced HIV-1-infected patients. Elvitegravir (EVG) is in late phases of clinical development. Since significant cross-resistance between RAL and EVG is observed, there is a need for second-generation integrase inhibitors (INIs) with a higher genetic barrier and limited cross-resistance to RAL/EVG. A panel of HIV-1 integrase recombinants, derived from plasma samples from raltegravir-treated patients (baseline and follow-up samples), were used to study the cross-resistance profile of two second-generation integrase inhibitors, MK-2048 and compound G. Samples with Q148H/R mutations had elevated fold change values with all compounds tested. Although samples with the Y143R/C mutation had reduced susceptibility to RAL, they remained susceptible to MK-2048 and compound G. Samples with the N155H mutation had no reduced susceptibility to compound G. In conclusion, our results allowed ranking of the INIs on the basis of the antiviral activities using recombinant virus stocks from RAL-treated patient viruses. The order according to decreasing susceptibility is compound G, MK-2048, and EVG. |
| Databáze: | OpenAIRE |
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