Document Detail


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.
MedLine Citation:
PMID:  20854144     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lotke Tambuyzer; Johan Vingerhoets; Hilde Azijn; Bjorn Daems; Steven Nijs; Marie-Pierre de Béthune; Gastón Picchio
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-20
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  26     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-18     Completed Date:  2010-12-21     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1197-205     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution / genetics
Anti-HIV Agents / administration & dosage*
Antiretroviral Therapy, Highly Active / methods*
Clinical Trials, Phase III as Topic
Drug Resistance, Viral*
HIV Envelope Protein gp41 / administration & dosage
HIV Infections / drug therapy*,  virology*
HIV Reverse Transcriptase / genetics
HIV-1 / drug effects,  genetics*,  isolation & purification
Humans
Microbial Sensitivity Tests
Mutation, Missense
Peptide Fragments / administration & dosage
Pyridazines / administration & dosage*
Randomized Controlled Trials as Topic
Ritonavir / administration & dosage
Sequence Analysis, DNA
Sulfonamides / administration & dosage
Treatment Failure
Viral Load
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/HIV Envelope Protein gp41; 0/Peptide Fragments; 0/Pyridazines; 0/Sulfonamides; 0C50HW4FO1/etravirine; 19OWO1T3ZE/enfuvirtide; EC 2.7.7.-/reverse transcriptase, Human immunodeficiency virus 1; EC 2.7.7.49/HIV Reverse Transcriptase; O3J8G9O825/Ritonavir; YO603Y8113/darunavir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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