Factors associated with the development of drug resistance mutations in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy in South Africa

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dc.contributor.author Rossouw, Theresa M.
dc.contributor.author Feucht, Ute Dagmar
dc.contributor.author Melikian, George
dc.contributor.author Van Dyk, Gisela
dc.contributor.author Thomas, Winifred Nancy
dc.contributor.author Du Plessis, Nicolette Marie
dc.contributor.author Avenant, Theunis Johannes
dc.date.accessioned 2015-08-28T08:23:58Z
dc.date.available 2015-08-28T08:23:58Z
dc.date.issued 2015-07-21
dc.description All files are available from the GenBank database under accession numbers KT031999-KT032063. en_ZA
dc.description Ms LAW Hahne for the development of the electronic database for the Kalafong clinic. Mr T Moto for the assistance with data collection. Drs G Malherbe and P Mahasha for assisting with the development of the genotyping assay and the staff at the HIV clinics for their dedicated service to patients and their assistance with data collection. en_ZA
dc.description Conceived and designed the experiments: TR UF. Performed the experiments: GVD. Analyzed the data: GM. Contributed reagents/materials/analysis tools: TR GM. Wrote the paper: TR UF GM GVD WT NDP TA. en_ZA
dc.description.abstract OBJECTIVE Limited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors. METHODS Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis. RESULTS The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;- 2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033). CONCLUSION Major protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed. en_ZA
dc.description.librarian am2015 en_ZA
dc.description.sponsorship This research and selected researchers (TR and GVD) were partially funded by a grant from the Delegation of the European Union to South Africa: "Drug Resistance Surveillance and Treatment Monitoring Network for the Public Sector HIV Antiretroviral Treatment Programme in the Free State” - Sante 2007/147-790 - and National Research Council of South Africa, Unlocking the Future 61509. en_ZA
dc.description.uri http://www.plosone.org en_ZA
dc.identifier.citation Rossouw TM, Feucht UD, Melikian G, van Dyk G, Thomas W, du Plessis NM, et al. (2015) Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa. PLoS ONE 10(7): e0133452. DOI: 10.1371/journal.pone.0133452. en_ZA
dc.identifier.issn 1932-6203
dc.identifier.other 10.1371/journal.pone.0133452
dc.identifier.uri http://hdl.handle.net/2263/49637
dc.language.iso en en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights © 2015 Rossouw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.subject Antiretroviral drug resistance en_ZA
dc.subject HIV-1 en_ZA
dc.subject Infected children en_ZA
dc.subject Antiretroviral therapy (ART) en_ZA
dc.subject Human immunodeficiency virus (HIV) en_ZA
dc.title Factors associated with the development of drug resistance mutations in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy in South Africa en_ZA
dc.type Article en_ZA


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