Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing

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dc.contributor.authorBansode, Vijay
dc.contributor.authorMcCormack, Grace P.
dc.contributor.authorShrestha, Ram K.
dc.contributor.authorTravers, Simon A.
dc.contributor.authorCrampin, Amelia C.
dc.contributor.authorNgwira, Bagrey
dc.contributor.authorFrench, Neil
dc.contributor.authorGlynn, Judith R.
dc.date.accessioned2017-07-12T12:47:43Z
dc.date.available2017-07-12T12:47:43Z
dc.date.issued2013
dc.description.abstractBACKGROUND: The role of HIV-1 RNA in the emergence of resistance to antiretroviral therapies (ARTs) is well documented while less is known about the role of historical viruses stored in the proviral DNA. The primary focus of this work was to characterize the genetic diversity and evolution of HIV drug resistant variants in an individual’s provirus during antiretroviral therapy using next generation sequencing. METHODS: Blood samples were collected prior to antiretroviral therapy exposure and during the course of treatment from five patients in whom drug resistance mutations had previously been identified using consensus sequencing. The spectrum of viral variants present in the provirus at each sampling time-point were characterized using 454 pyrosequencing from multiple combined PCR products. The prevalence of viral variants containing drug resistant mutations (DRMs) was characterized at each time-point. RESULTS: Low abundance drug resistant viruses were identified in 14 of 15 sampling time-points from the five patients. In all individuals DRMs against current therapy were identified at one or more of the sampling time-points. In two of the five individuals studied these DRMs were present prior to treatment exposure and were present at high prevalence within the amplified and sequenced viral population. DRMs to drugs other than those being currently used were identified in four of the five individuals. CONCLUSION: The presence of DRMs in the provirus, regardless of their observed prevalence did not appear to have an effect on clinical outcomes in the short term suggesting that the drug resistant viral variants present in the proviral DNA do not appear to play a role in the short term in facilitating the emergence of drug resistance.en_US
dc.description.accreditationDepartment of HE and Training approved list
dc.identifier.citationBansode, V. et al. (2013). Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing. BMC Infectious Diseases, 13 (52): 1-9en_US
dc.identifier.issn1471-2334
dc.identifier.urihttp://hdl.handle.net/10566/3066
dc.language.isoenen_US
dc.publisherBioMed Central -The Open Access Publisheren_US
dc.rightsCopyright Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttp://dx.doi.org/10.1186/1471-2334-13-52
dc.subjectHIV-1en_US
dc.subjectDrug resistanceen_US
dc.subjectSubtype Cen_US
dc.subjectMalawien_US
dc.subjectUltradeep sequencingen_US
dc.subjectProviral DNAen_US
dc.titleCharacterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencingen_US
dc.typeArticleen_US

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