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Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia

2015; Wiley; Volume: 87; Issue: 7 Linguagem: Inglês

10.1002/jmv.24162

1096-9071

Lillian Seu, Lloyd Mulenga, Mpanji Siwingwa, Izukanji Sikazwe, Nason Lambwe, M. Bradford Guffey, H. Benjamin,

HIV Research and Treatment

Journal of Medical VirologyVolume 87, Issue 7 p. 1149-1157 Research Article Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia Lillian Seu, Corresponding Author Lillian Seu School of Medicine, University of Alabama at Birmingham, Alabama Centre for Infectious Disease Research Zambia, Lusaka, Zambia Correspondence to: Lillian Seu, University of Alabama at Birmingham, 845 19th Street South, Birmingham 35294, Alabama. E-mail: [email protected]Search for more papers by this authorLloyd B. Mulenga, Lloyd B. Mulenga Adult Infectious Diseases Centre, University Teaching Hospital, Lusaka, Zambia School of Medicine, University of Zambia, Lusaka, ZambiaSearch for more papers by this authorMpanji Siwingwa, Mpanji Siwingwa Centre for Infectious Disease Research Zambia, Lusaka, ZambiaSearch for more papers by this authorIzukanji Sikazwe, Izukanji Sikazwe Centre for Infectious Disease Research Zambia, Lusaka, ZambiaSearch for more papers by this authorNason Lambwe, Nason Lambwe Adult Infectious Diseases Centre, University Teaching Hospital, Lusaka, Zambia School of Medicine, University of Zambia, Lusaka, ZambiaSearch for more papers by this authorM. Bradford Guffey, M. Bradford Guffey School of Medicine, University of Alabama at Birmingham, Alabama Centre for Infectious Disease Research Zambia, Lusaka, ZambiaSearch for more papers by this authorBenjamin H. Chi, Benjamin H. Chi Centre for Infectious Disease Research Zambia, Lusaka, Zambia Schools of Medicine and Public Health, University of North Carolina at Chapel Hill, North CarolinaSearch for more papers by this author Lillian Seu, Corresponding Author Lillian Seu School of Medicine, University of Alabama at Birmingham, Alabama Centre for Infectious Disease Research Zambia, Lusaka, Zambia Correspondence to: Lillian Seu, University of Alabama at Birmingham, 845 19th Street South, Birmingham 35294, Alabama. E-mail: [email protected]Search for more papers by this authorLloyd B. Mulenga, Lloyd B. Mulenga Adult Infectious Diseases Centre, University Teaching Hospital, Lusaka, Zambia School of Medicine, University of Zambia, Lusaka, ZambiaSearch for more papers by this authorMpanji Siwingwa, Mpanji Siwingwa Centre for Infectious Disease Research Zambia, Lusaka, ZambiaSearch for more papers by this authorIzukanji Sikazwe, Izukanji Sikazwe Centre for Infectious Disease Research Zambia, Lusaka, ZambiaSearch for more papers by this authorNason Lambwe, Nason Lambwe Adult Infectious Diseases Centre, University Teaching Hospital, Lusaka, Zambia School of Medicine, University of Zambia, Lusaka, ZambiaSearch for more papers by this authorM. Bradford Guffey, M. Bradford Guffey School of Medicine, University of Alabama at Birmingham, Alabama Centre for Infectious Disease Research Zambia, Lusaka, ZambiaSearch for more papers by this authorBenjamin H. Chi, Benjamin H. Chi Centre for Infectious Disease Research Zambia, Lusaka, Zambia Schools of Medicine and Public Health, University of North Carolina at Chapel Hill, North CarolinaSearch for more papers by this author First published: 05 March 2015 https://doi.org/10.1002/jmv.24162Citations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract In settings of resource constraint, an understanding of HIV drug resistance can guide antiretroviral therapy (ART) at switch to second-line therapy. To determine the prevalence of such HIV drug resistance mutations (HIV DRM), we used an in-house sequencing assay in the pol gene (protease and partial reverse transcriptase) in a cohort of patients suspected of failing a first-line regimen, which in Zambia comprises two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI). Our analysis cohort (n = 68) was referred to the University Teaching Hospital in Lusaka from November 2009 to October 2012. Median duration on first-line ART to suspected treatment failure was 3.2 years (IQR 1.7–4.7 years). The majority of patients (95%) harbored HIV-1 subtype C virus. Analysis of reverse transcriptase revealed M184V (88%), K103N/S (32%), and Y181C/I/V (41%) DRMs, with the latter conferring reduced susceptibility to the salvage therapy candidates etravirine and rilpivirine. Three patients (5%) had major protease inhibitor (PI) resistance mutations: all three had the V82A mutation, and one patient (Clade J virus) had a concurrent M46I, Q58E, and L76V DRM. HIV-1 genotyping revealed major and minor DRMs as well as high levels of polymorphisms in subtype C isolates from patients failing first-line antiretroviral therapy. Closer monitoring of DRM mutations at first-line failure can inform clinicians about future options for salvage therapy. J. Med. Virol. 87:1149–1157, 2015. © 2015 Wiley Periodicals, Inc. Citing Literature Supporting Information Additional supporting information may be found in the online version of this article at the publisher's web-site. Filename Description jmv24162-sup-0001-SupFig-S1.tif559.2 KB Supporting Information Figure S1: Environmental applications of organoclays for sorption of phenol and its derivatives Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume87, Issue7July 2015Pages 1149-1157 RelatedInformation