Decreased Phenotypic Susceptibility to Etravirine in Patients with Predicted Genotypic Sensitivity
Agneskog, Eva (Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden)
Nowak, Piotr (Karolinska Institutet (Estocolm, Suècia))
Maijgren Steffensson, Catharina (Karolinska Institutet (Estocolm, Suècia))
Casadellà, Maria (IrsiCaixa)
Noguera-Julian, Marc (IrsiCaixa)
Paredes, Roger (IrsiCaixa)
Källander, Clas F. R. (Cavidi AB, Uppsala, Sweden)
Sönnerborg, Anders (Karolinska Institutet (Estocolm, Suècia))

Data:	2014
Resum:	A sensitive, phenotypic reverse transcriptase (RT)-based drug susceptibility assay for the detection of etravirine (ETR) resistance in patient isolates was developed and compared with the results from direct sequencing and ultra-deep pyrosequencing (UDPS). Samples were obtained from 15 patients with antiretroviral therapy (ART) failure and from five non-nucleoside reverse transcriptase inhibitor (NNRTI)-naïve patients of whom four were infected by an NNRTI-resistant strain (transmitted drug resistance, TDR). In five patients, two consecutive samples (a and b) were taken for follow up of the virological response. HIV-1 RT was purified and drug susceptibility (IC) to ETR was estimated. Direct sequencing was performed in all samples and UDPS in samples from nine patients. Increased IC to ETR was found in samples from 13 patients where direct sequencing predicted resistance in only four. UDPS identified additional (N = 11) NNRTI resistance associated mutations (RAMs) in six of nine tested patients. During early failure, IC increases were observed in three of six patients without any ETR-RAMs detected by direct sequencing. In further two patients, who stopped NNRTI before sampling, increased IC values were found shortly after, despite absence of ETR-RAMs. In two patients who had stopped NNRTI for.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 9 (july 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0101508
PMID: 25000302

9 p, 212.0 KB

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