It is time to consider third-line options in antiretroviral-experienced paediatric patients?

 

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dc.contributor.author van Zyl, Gert en_ZA
dc.contributor.author Rabie, Helena en_ZA
dc.contributor.author Nuttall, James en_ZA
dc.contributor.author Cotton, Mark en_ZA
dc.date.accessioned 2015-11-18T03:58:50Z
dc.date.available 2015-11-18T03:58:50Z
dc.date.issued 2011 en_ZA
dc.identifier.citation Van Zyl, G. U., Rabie, H., Nuttall, J. J., & Cotton, M. F. (2011). It is time to consider third-line options in antiretroviral-experienced paediatric patients?. Journal of the International AIDS Society, 14(1), 55. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15085
dc.identifier.uri http://dx.doi.org/10.1186/1758-2652-14-55
dc.description.abstract BACKGROUND: The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations. METHODS: In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations. RESULTS: Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance. CONCLUSIONS: In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy. en_ZA
dc.language.iso eng en_ZA
dc.publisher BioMed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_ZA
dc.source Journal of the International AIDS Society en_ZA
dc.source.uri http://www.biomedcentral.com/1758-2652/ en_ZA
dc.subject.other full-dose ritonavir en_ZA
dc.subject.other South African children en_ZA
dc.title It is time to consider third-line options in antiretroviral-experienced paediatric patients? en_ZA
dc.type Journal Article en_ZA
dc.rights.holder 2011 van Zyl et al; licensee BioMed Central Ltd. 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 Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation van Zyl, G., Rabie, H., Nuttall, J., & Cotton, M. (2011). It is time to consider third-line options in antiretroviral-experienced paediatric patients?. <i>Journal of the International AIDS Society</i>, http://hdl.handle.net/11427/15085 en_ZA
dc.identifier.chicagocitation van Zyl, Gert, Helena Rabie, James Nuttall, and Mark Cotton "It is time to consider third-line options in antiretroviral-experienced paediatric patients?." <i>Journal of the International AIDS Society</i> (2011) http://hdl.handle.net/11427/15085 en_ZA
dc.identifier.vancouvercitation van Zyl G, Rabie H, Nuttall J, Cotton M. It is time to consider third-line options in antiretroviral-experienced paediatric patients?. Journal of the International AIDS Society. 2011; http://hdl.handle.net/11427/15085. en_ZA
dc.identifier.ris TY - Journal Article AU - van Zyl, Gert AU - Rabie, Helena AU - Nuttall, James AU - Cotton, Mark AB - BACKGROUND: The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations. METHODS: In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations. RESULTS: Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance. CONCLUSIONS: In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy. DA - 2011 DB - OpenUCT DO - 10.1186/1758-2652-14-55 DP - University of Cape Town J1 - Journal of the International AIDS Society LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - It is time to consider third-line options in antiretroviral-experienced paediatric patients? TI - It is time to consider third-line options in antiretroviral-experienced paediatric patients? UR - http://hdl.handle.net/11427/15085 ER - en_ZA


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