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

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dc.contributor.authorvan Zyl, Gerten_ZA
dc.contributor.authorRabie, Helenaen_ZA
dc.contributor.authorNuttall, Jamesen_ZA
dc.contributor.authorCotton, Marken_ZA
dc.date.accessioned2015-11-18T03:58:50Z
dc.date.available2015-11-18T03:58:50Z
dc.date.issued2011en_ZA
dc.description.abstractBACKGROUND: 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.identifier.apacitationvan 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/11427/15085en_ZA
dc.identifier.chicagocitationvan 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/11427/15085en_ZA
dc.identifier.citationVan 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.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
dc.identifier.urihttp://hdl.handle.net/11427/15085
dc.identifier.urihttp://dx.doi.org/10.1186/1758-2652-14-55
dc.identifier.vancouvercitationvan 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.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_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 Licenseen_ZA
dc.rights.holder2011 van Zyl et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceJournal of the International AIDS Societyen_ZA
dc.source.urihttp://www.biomedcentral.com/1758-2652/en_ZA
dc.subject.otherfull-dose ritonaviren_ZA
dc.subject.otherSouth African childrenen_ZA
dc.titleIt is time to consider third-line options in antiretroviral-experienced paediatric patients?en_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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