No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial

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dc.contributor.authorChopera, Denis Ren_ZA
dc.contributor.authorMann, Jaclyn Ken_ZA
dc.contributor.authorMwimanzi, Philipen_ZA
dc.contributor.authorOmarjee, Salehaen_ZA
dc.contributor.authorKuang, Xiaomei Ten_ZA
dc.contributor.authorNdabambi, Nonkululekoen_ZA
dc.contributor.authorGoodier, Sarahen_ZA
dc.contributor.authorMartin, Ericen_ZA
dc.contributor.authorNaranbhai, Viveken_ZA
dc.contributor.authorKarim, Salim Abdoolen_ZA
dc.date.accessioned2016-01-11T06:48:43Z
dc.date.available2016-01-11T06:48:43Z
dc.date.issued2013en_ZA
dc.description.abstractBACKGROUND: Use of antiretroviral-based microbicides for HIV-1 prophylaxis could introduce a transmission barrier that inadvertently facilitates the selection of fitter viral variants among incident infections. To investigate this, we assessed the in vitro function of gag-protease and nef sequences from participants who acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial. Methods and RESULTS: We isolated the earliest available gag-protease and nef gene sequences from 83 individuals and examined their in vitro function using recombinant viral replication capacity assays and surface protein downregulation assays, respectively. No major phylogenetic clustering and no significant differences in gag-protease or nef function were observed in participants who received tenofovir gel versus placebo gel prophylaxis. CONCLUSION: Results indicate that the partial protective effects of 1% tenofovir gel use in the CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1 variants with enhanced Gag-Protease or Nef fitness.en_ZA
dc.identifier.apacitationChopera, D. R., Mann, J. K., Mwimanzi, P., Omarjee, S., Kuang, X. T., Ndabambi, N., ... Karim, S. A. (2013). No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial. <i>PLoS One</i>, http://hdl.handle.net/11427/16229en_ZA
dc.identifier.chicagocitationChopera, Denis R, Jaclyn K Mann, Philip Mwimanzi, Saleha Omarjee, Xiaomei T Kuang, Nonkululeko Ndabambi, Sarah Goodier, Eric Martin, Vivek Naranbhai, and Salim Abdool Karim "No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/16229en_ZA
dc.identifier.citationChopera, D. R., Mann, J. K., Mwimanzi, P., Omarjee, S., Kuang, X. T., Ndabambi, N., ... & Abdool Karim, Q. (2013). No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial. PloS one, 8(8), e71758. doi:10.1371/journal.pone.0071758en_ZA
dc.identifier.ris TY - Journal Article AU - Chopera, Denis R AU - Mann, Jaclyn K AU - Mwimanzi, Philip AU - Omarjee, Saleha AU - Kuang, Xiaomei T AU - Ndabambi, Nonkululeko AU - Goodier, Sarah AU - Martin, Eric AU - Naranbhai, Vivek AU - Karim, Salim Abdool AB - BACKGROUND: Use of antiretroviral-based microbicides for HIV-1 prophylaxis could introduce a transmission barrier that inadvertently facilitates the selection of fitter viral variants among incident infections. To investigate this, we assessed the in vitro function of gag-protease and nef sequences from participants who acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial. Methods and RESULTS: We isolated the earliest available gag-protease and nef gene sequences from 83 individuals and examined their in vitro function using recombinant viral replication capacity assays and surface protein downregulation assays, respectively. No major phylogenetic clustering and no significant differences in gag-protease or nef function were observed in participants who received tenofovir gel versus placebo gel prophylaxis. CONCLUSION: Results indicate that the partial protective effects of 1% tenofovir gel use in the CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1 variants with enhanced Gag-Protease or Nef fitness. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0071758 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial TI - No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial UR - http://hdl.handle.net/11427/16229 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16229
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0071758
dc.identifier.vancouvercitationChopera DR, Mann JK, Mwimanzi P, Omarjee S, Kuang XT, Ndabambi N, et al. No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial. PLoS One. 2013; http://hdl.handle.net/11427/16229.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Virologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Chopera et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherViral replicationen_ZA
dc.subject.otherCloningen_ZA
dc.subject.otherMicrobicidesen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherNatural selectionen_ZA
dc.subject.otherProphylaxisen_ZA
dc.subject.otherSequence analysisen_ZA
dc.titleNo evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trialen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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