Characterization of Genotypic and Phenotypic Changes in HIV-1-Infected Patients with Virologic Failure on an Etravirine-Containing Regimen in the DUET-1 and DUET-2 Clinical Studies
| Autor: | Johan Vingerhoets, Bjorn Daems, Lotke Tambuyzer, Steven Nijs, Gaston Picchio, Marie Pierre de Béthune, Hilde Azijn |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Oncology
medicine.medical_specialty Enfuvirtide Anti-HIV Agents Immunology Mutation Missense Etravirine HIV Infections Microbial Sensitivity Tests Nucleoside Reverse Transcriptase Inhibitor Antiretroviral Therapy Highly Active Virology Internal medicine Drug Resistance Viral Nitriles medicine Humans Treatment Failure Sida Darunavir Randomized Controlled Trials as Topic Sulfonamides Ritonavir biology Reverse-transcriptase inhibitor business.industry Sequence Analysis DNA Viral Load biology.organism_classification HIV Envelope Protein gp41 HIV Reverse Transcriptase Peptide Fragments Pyridazines Regimen Pyrimidines Infectious Diseases Amino Acid Substitution Clinical Trials Phase III as Topic HIV-1 business medicine.drug |
| Zdroj: | AIDS Research and Human Retroviruses. 26:1197-1205 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2009.0302 |
| Popis: | The randomized, placebo-controlled Phase III DUET studies enrolled treatment-experienced, HIV-1-infected patients. We examined the genotypic and phenotypic changes at endpoint relative to baseline, including the emergence of individual reverse transcriptase (RT) mutations, in patients who received the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine and experienced virologic failure by rebound by the time of the Week 96 analysis. Patients received etravirine 200 mg twice-daily in combination with a background regimen containing darunavir/ritonavir, investigator-selected nucleoside reverse transcriptase inhibitors, and optional enfuvirtide. Virologic failure by rebound occurred in 93 (15.5%) etravirine-treated patients (compared with 170 [28.1%] placebo-treated patients). Patients experiencing virologic failure had more baseline antiretroviral resistance and lower activity of the background regimen relative to those not experiencing failure. Emergence of NNRTI resistance-associated mutations was observed in 55 of 93 patients. The most frequently emerging RT mutations were V179F, V179I, and Y181C, with positions K101 and E138 also showing frequent changes. Mutations usually emerged in a background of multiple other NNRTI mutations and were, in most cases, associated with a decrease in phenotypic sensitivity to etravirine at endpoint. Further analysis is needed to clarify the role of mutations at position 138 as determinants of etravirine resistance. |
| Databáze: | OpenAIRE |
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