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

 

Show simple item record

dc.contributor.author Levison, Julie H en_ZA
dc.contributor.author Orrell, Catherine en_ZA
dc.contributor.author Gallien, Sébastien en_ZA
dc.contributor.author Kuritzkes, Daniel R en_ZA
dc.contributor.author Fu, Naishin en_ZA
dc.contributor.author Losina, Elena en_ZA
dc.contributor.author Freedberg, Kenneth A en_ZA
dc.contributor.author Wood, Robin en_ZA
dc.date.accessioned 2015-12-20T16:03:49Z
dc.date.available 2015-12-20T16:03:49Z
dc.date.issued 2012 en_ZA
dc.identifier.citation Levison, 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.0032144 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15909
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0032144
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Antiretroviral therapy en_ZA
dc.subject.other HIV-1 en_ZA
dc.subject.other HIV en_ZA
dc.subject.other Mutation detection en_ZA
dc.subject.other RNA sequencing en_ZA
dc.subject.other Microbial mutation en_ZA
dc.subject.other Drug therapy en_ZA
dc.subject.other South Africa en_ZA
dc.title Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2012 Levison et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Desmond Tutu HIV Centre en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Levison, 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/11427/15909 en_ZA
dc.identifier.chicagocitation Levison, 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/11427/15909 en_ZA
dc.identifier.vancouvercitation Levison 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.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


Files in this item

This item appears in the following Collection(s)

Show simple item record

This 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. Except where otherwise noted, this item's license is described as This 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.