Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa

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dc.contributor.authorLevison, Julie Hen_ZA
dc.contributor.authorOrrell, Catherineen_ZA
dc.contributor.authorGallien, Sébastienen_ZA
dc.contributor.authorKuritzkes, Daniel Ren_ZA
dc.contributor.authorFu, Naishinen_ZA
dc.contributor.authorLosina, Elenaen_ZA
dc.contributor.authorFreedberg, Kenneth Aen_ZA
dc.contributor.authorWood, Robinen_ZA
dc.date.accessioned2015-12-20T16:03:49Z
dc.date.available2015-12-20T16:03:49Z
dc.date.issued2012en_ZA
dc.description.abstractBACKGROUND: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal FINDINGS: HIV-infected patients ≥15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.en_ZA
dc.identifier.apacitationLevison, J. H., Orrell, C., Gallien, S., Kuritzkes, D. R., Fu, N., Losina, E., ... Wood, R. (2012). Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa. <i>PLoS One</i>, http://hdl.handle.net/11427/15909en_ZA
dc.identifier.chicagocitationLevison, Julie H, Catherine Orrell, Sébastien Gallien, Daniel R Kuritzkes, Naishin Fu, Elena Losina, Kenneth A Freedberg, and Robin Wood "Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/15909en_ZA
dc.identifier.citationLevison, J. H., Orrell, C., Gallien, S., Kuritzkes, D. R., Fu, N., Losina, E., ... & Wood, R. (2011). Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa. PloS one, 7(3), e32144. doi:10.1371/journal.pone.0032144en_ZA
dc.identifier.ris TY - Journal Article AU - Levison, Julie H AU - Orrell, Catherine AU - Gallien, Sébastien AU - Kuritzkes, Daniel R AU - Fu, Naishin AU - Losina, Elena AU - Freedberg, Kenneth A AU - Wood, Robin AB - BACKGROUND: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal FINDINGS: HIV-infected patients ≥15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0032144 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa TI - Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa UR - http://hdl.handle.net/11427/15909 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15909
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0032144
dc.identifier.vancouvercitationLevison JH, Orrell C, Gallien S, Kuritzkes DR, Fu N, Losina E, et al. Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa. PLoS One. 2012; http://hdl.handle.net/11427/15909.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDesmond Tutu HIV Centreen_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© 2012 Levison 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.otherAntiretroviral therapyen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherMutation detectionen_ZA
dc.subject.otherRNA sequencingen_ZA
dc.subject.otherMicrobial mutationen_ZA
dc.subject.otherDrug therapyen_ZA
dc.subject.otherSouth Africaen_ZA
dc.titleVirologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africaen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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