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Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene

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dc.contributor.author Jallow, S. en_US
dc.contributor.author Kaye, S. en_US
dc.contributor.author Schutten, M. en_US
dc.contributor.author Brandin, E. en_US
dc.contributor.author Albert, J. en_US
dc.contributor.author McConkey, S. J. en_US
dc.contributor.author Corrah, T. en_US
dc.contributor.author Whittle, H. en_US
dc.contributor.author Vanham, G. en_US
dc.contributor.author Rowland-Jones, S. en_US
dc.contributor.author Janssens, W. en_US
dc.date.accessioned 2007-12-06T14:47:10Z
dc.date.available 2007-12-06T14:47:10Z
dc.date.issued 2007 en_US
dc.identifier.issn 0095-1137 en_US
dc.identifier.doi http://dx.doi.org/10.1128/JCM.02220-06
dc.identifier.other ITG-M1B en_US
dc.identifier.other ITG-M9A en_US
dc.identifier.other ITG-MLA en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-VIROL en_US
dc.identifier.other JIF en_US
dc.identifier.other DOI en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.uri http://hdl.handle.net/10390/1793
dc.description.abstract Human immunodeficiency virus type 2 (HIV-2) is naturally resistant to several antiretroviral drugs, including all of the non-nucleoside reverse transcriptase inhibitors and the entry inhibitor T-20, and may have reduced susceptibility to some protease inhibitors. These resistance properties make treatment of HIV-2 patients difficult, with very limited treatment options. Therefore, early detection of resistance mutations is important for understanding treatment failures and guiding subsequent therapy decisions. With the Global Fund Initiative, a substantial number of HIV-2 patients in West Africa will receive antiretroviral therapy. Therefore, development of cheaper and more sustainable resistance assays, such as the oligonucleotide ligation assay (OLA), is a priority. In this study, we designed oligonucleotide probes to detect the Q151M mutation, associated with phenotypic resistance to zidovudine, didanosine, zalcitabine, and stavudine, and the M184V mutation, associated with phenotypic resistance to lamivudine and emtricitabine, in HIV-2. The assay was successfully developed and evaluated with 122 samples from The Gambia, Guinea Bissau, The Netherlands, and Sweden. The overall sensitivity of the assay was 98.8%, with 99.2% for Q151M and 98.4% for M184V. OLA results were compared with sequencing to give high concordances of 98.4% (Q151M) and 97.5% (M184V). OLA demonstrated a higher sensitivity for detection of minor variants as a mixture of wild-type and mutant viruses in cases when sequencing detected only the major population. In conclusion, we have developed a simple, easy-to-use, and economical assay for genotyping of drug resistance in HIV-2 that is more sustainable for use in resource-poor settings than is consensus sequencing. en_US
dc.language English en_US
dc.publisher American Society for Microbiology en_US
dc.subject Virology en_US
dc.subject HIV-2 en_US
dc.subject Drug resistance en_US
dc.subject Mutations en_US
dc.subject Drug sensitivity testing en_US
dc.subject Genotyping en_US
dc.subject Oligonucleotide probes en_US
dc.subject Sustainability en_US
dc.subject Developing countries en_US
dc.title Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene en_US
dc.type Article en_US
dc.citation.issue 5 en_US
dc.citation.jtitle Journal of Clinical Microbiology en_US
dc.citation.volume 45 en_US
dc.citation.pages 1565-1571 en_US
dc.publisher.place Washington en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/17329450
dc.citation.jabbreviation J Clin Microbiol en_US


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