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Natural residues versus antiretroviral drug-selected mutations in HIV type 1 group O reverse transcriptase and protease related to virological drug failure in vivo

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Show simple item record De Baar, M. P. en_US Janssens, W. en_US De Ronde, A. en_US Fransen, K. en_US Colebunders, R. en_US Kestens, L. en_US van der Groen, G. en_US Goudsmit, J. en_US 2007-12-06T14:46:46Z 2007-12-06T14:46:46Z 2000 en_US
dc.identifier.issn 0889-2229 en_US
dc.identifier.other ITG-M2A en_US
dc.identifier.other ITG-M4A en_US
dc.identifier.other ITG-C5A en_US
dc.identifier.other ITG-M6A en_US
dc.identifier.other ITG-M7A en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-VIROL en_US
dc.identifier.other CLINIC en_US
dc.identifier.other U-HIVCLI en_US
dc.identifier.other JIF en_US
dc.identifier.other DOI en_US
dc.identifier.other MULTI en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.other FTA
dc.description.abstract HIV-1 group O viruses were first recognized as a distinct subgroup of HIV-1 with the isolation and characterization in 1990 of a virus (ANT70) from a woman (individual A) and her spouse (individual B), both from Cameroon (De Leys R, et al.: J Virol 1990;64:1207-1216). During the 5-6 years before treatment, individual A remained asymptomatic, with viral RNA levels between 2.5 and 2.8 log10 copies/ml, as measured by a newly developed group O-specific quantitative NASBA-based RNA assay. Individual B developed mild clinical symptoms, with 3.1 to 3.6 log10 copies of viral RNA per milliliter. HIV-1 sequences obtained from both individuals showed pretreatment residues in protease that confer resistance to protease inhibitors in group M viruses (10I, 36I, and 71V). Individual A showed an initial response to AZT, but shortly after addition of ddC and saquinavir, the RNA levels returned to baseline, while subsequent treatment with d4T, 3TC, and indinavir reduced the RNA level to less than 50 copies/ml for the time of follow-up. Individual B showed no response to AZT or ddC monotherapy, and a change to d4T, 3TC, and indinavir had, in contrast to individual A, only a temporary effect. While a multitude of mutations in HIV-1 group O reverse transcriptase (RT) and protease appeared that are associated with drug resistance in group M viruses, the observed T215N mutation in RT and the V15I and V22A mutations in protease have not previously been described and may represent resistance-conferring mutations specific to group O viruses. These results indicate that treatment of HIV-1 group O-infected individuals with antiretroviral drug regimens that include protease inhibitors might lead to rapid selection for resistance-conferring mutations. This probably results from preexisting protease residues contributing to reduced sensitivity of group O viruses to protease inhibitors, as is observed in vitro. en_US
dc.language English en_US
dc.subject Viral diseases en_US
dc.subject HIV-1 group O en_US
dc.subject Reverse transcriptase en_US
dc.subject Protease en_US
dc.subject Mutations en_US
dc.title Natural residues versus antiretroviral drug-selected mutations in HIV type 1 group O reverse transcriptase and protease related to virological drug failure in vivo en_US
dc.type Article en_US
dc.citation.issue 14 en_US
dc.citation.jtitle AIDS Research and Human Retroviruses en_US
dc.citation.volume 16 en_US
dc.citation.pages 1385-1394 en_US
dc.citation.jabbreviation AIDS Res Hum Retroviruses en_US

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