Virologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort study

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dc.contributor.advisorDavies, Mary-Annen_ZA
dc.contributor.advisorNuttall Jamesen_ZA
dc.contributor.authorReichmuth, Kirsten Leahen_ZA
dc.date.accessioned2015-10-19T07:46:45Z
dc.date.available2015-10-19T07:46:45Z
dc.date.issued2015en_ZA
dc.description.abstractMajor advances have been made in preventing mother to child transmission of HIV (PMTCT), as well as in decreasing morbidity and mortality amongst HIV-infected infants and children. However, maintenance of excellent adherence to combination antiretroviral therapy (cART) lifelong is required to achieve optimal benefits. In addition, treatment options for children are limited by potential drug-resistance following PMTCT exposure, availability of appropriate and palatable formulations, long-term toxicity concerns and drug-interactions - notably with co-treatment for tuberculosis. Given these challenges, drug simplification strategies for children remains an important area of research. The World Health Organisation (WHO) recommends lopinavir/ritonavir-based (LPV/r) cART as first-line for children <36 months old with the option to substitute LPV/r with a non-nucleoside reverse transcriptase inhibitor if virologic suppression is maintained. This simplification strategy is potentially cost-saving, regimen-sparing and more tolerable, with a better long-term side-effect profile. Consequently, benefits should also exist in terms of adherence. The main evidence in support of this strategy has come from trials conducted by the Nevirapine Resistance Studies (NEVEREST) group. In particular, the NEVEREST 3 trial showed that substituting LPV/r for efavirenz (EFV) in children aged 36-60 months virologically suppressed on LPV/r-based cART was protective against viral rebound and had no effect on virological failure compared with remaining on LPV/r. To our knowledge, no studies to date have examined the virologic outcomes of children changed to an EFV-based regimen after initiating a LPV/r based regimen in routine, resource-constrained settings where selection of patients as eligible for EFV substitution and subsequent monitoring practices may be less rigorous than in a trial setting. At the International Epidemiologic Database to Evaluate AIDS - Southern Africa collaboration's (IeDEA-SA) South African sites LPV/r has been used for first-line cART in children <36 months of age irrespective of PMTCT antiretroviral exposure. At many of these sites clinicians have, at their discretion, elected to substitute LPV/r with EFV when children reach 36 months of age. This has provided the opportunity to conduct an observational study to investigate this practice in a routine-care setting – comparing outcomes in children virologically suppressed and ≥36 months old who underwent a substitution of LPV/r to EFV (substitution group) to those who remained on their initial LPV/r-based regimen (stay group).en_ZA
dc.identifier.apacitationReichmuth, K. L. (2015). <i>Virologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort study</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Public Health and Family Medicine. Retrieved from http://hdl.handle.net/11427/14257en_ZA
dc.identifier.chicagocitationReichmuth, Kirsten Leah. <i>"Virologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort study."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Public Health and Family Medicine, 2015. http://hdl.handle.net/11427/14257en_ZA
dc.identifier.citationReichmuth, K. 2015. Virologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort study. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Reichmuth, Kirsten Leah AB - Major advances have been made in preventing mother to child transmission of HIV (PMTCT), as well as in decreasing morbidity and mortality amongst HIV-infected infants and children. However, maintenance of excellent adherence to combination antiretroviral therapy (cART) lifelong is required to achieve optimal benefits. In addition, treatment options for children are limited by potential drug-resistance following PMTCT exposure, availability of appropriate and palatable formulations, long-term toxicity concerns and drug-interactions - notably with co-treatment for tuberculosis. Given these challenges, drug simplification strategies for children remains an important area of research. The World Health Organisation (WHO) recommends lopinavir/ritonavir-based (LPV/r) cART as first-line for children <36 months old with the option to substitute LPV/r with a non-nucleoside reverse transcriptase inhibitor if virologic suppression is maintained. This simplification strategy is potentially cost-saving, regimen-sparing and more tolerable, with a better long-term side-effect profile. Consequently, benefits should also exist in terms of adherence. The main evidence in support of this strategy has come from trials conducted by the Nevirapine Resistance Studies (NEVEREST) group. In particular, the NEVEREST 3 trial showed that substituting LPV/r for efavirenz (EFV) in children aged 36-60 months virologically suppressed on LPV/r-based cART was protective against viral rebound and had no effect on virological failure compared with remaining on LPV/r. To our knowledge, no studies to date have examined the virologic outcomes of children changed to an EFV-based regimen after initiating a LPV/r based regimen in routine, resource-constrained settings where selection of patients as eligible for EFV substitution and subsequent monitoring practices may be less rigorous than in a trial setting. At the International Epidemiologic Database to Evaluate AIDS - Southern Africa collaboration's (IeDEA-SA) South African sites LPV/r has been used for first-line cART in children <36 months of age irrespective of PMTCT antiretroviral exposure. At many of these sites clinicians have, at their discretion, elected to substitute LPV/r with EFV when children reach 36 months of age. This has provided the opportunity to conduct an observational study to investigate this practice in a routine-care setting – comparing outcomes in children virologically suppressed and ≥36 months old who underwent a substitution of LPV/r to EFV (substitution group) to those who remained on their initial LPV/r-based regimen (stay group). DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Virologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort study TI - Virologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort study UR - http://hdl.handle.net/11427/14257 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14257
dc.identifier.vancouvercitationReichmuth KL. Virologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort study. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Public Health and Family Medicine, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/14257en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Public Health and Family Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherPublic Healthen_ZA
dc.titleVirologic outcomes of HIV-infected children undergoing a single-class drug substitution from Lopinavir/Ritonavir- to Efavirenz-based antiretroviral treatment: A retrospective cohort studyen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMPHen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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