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Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Metzner Karin J, Scherrer Alexandra U, von Wyl Viktor, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Furrer Hansjakob, Hirsch Hans H, Vernazza Pietro L, Cavassini Matthias, Calmy Alexandra, Bernasconi Enos, Weber Rainer, Günthard Huldrych F,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal AIDS (London, England)
Volume (Issue) 28(15)
Page(s) 2231 - 9
Title of proceedings AIDS (London, England)
DOI 10.1097/qad.0000000000000397

Open Access

URL http://dx.doi.org/10.7892/boris.54921
Type of Open Access Repository (Green Open Access)

Abstract

The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.
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