Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis

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dc.contributor.authorRockwood, Neeshaen_ZA
dc.contributor.authorAbdullahi, Leila Hen_ZA
dc.contributor.authorWilkinson, Robert Jen_ZA
dc.contributor.authorMeintjes, Graemeen_ZA
dc.date.accessioned2015-12-20T16:05:19Z
dc.date.available2015-12-20T16:05:19Z
dc.date.issued2015en_ZA
dc.description.abstractBACKGROUND: Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies. METHODS: Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I 2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies. RESULTS: Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I 2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I 2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5 th to 95 th percentile 0.07 to 3.2%). CONCLUSION: Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies.en_ZA
dc.identifier.apacitationRockwood, N., Abdullahi, L. H., Wilkinson, R. J., & Meintjes, G. (2015). Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis. <i>PLoS One</i>, http://hdl.handle.net/11427/15921en_ZA
dc.identifier.chicagocitationRockwood, Neesha, Leila H Abdullahi, Robert J Wilkinson, and Graeme Meintjes "Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/15921en_ZA
dc.identifier.citationRockwood, N., Abdullahi, L. H., Wilkinson, R. J., & Meintjes, G. (2015). Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis. PloS one, 10(9), e0139017. doi:10.1371/journal.pone.0139017en_ZA
dc.identifier.ris TY - Journal Article AU - Rockwood, Neesha AU - Abdullahi, Leila H AU - Wilkinson, Robert J AU - Meintjes, Graeme AB - BACKGROUND: Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies. METHODS: Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I 2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies. RESULTS: Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I 2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I 2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5 th to 95 th percentile 0.07 to 3.2%). CONCLUSION: Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pone.0139017 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis TI - Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis UR - http://hdl.handle.net/11427/15921 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15921
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0139017
dc.identifier.vancouvercitationRockwood N, Abdullahi LH, Wilkinson RJ, Meintjes G. Risk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysis. PLoS One. 2015; http://hdl.handle.net/11427/15921.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_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 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2015 Rockwood et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherIsoniaziden_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherExtensively drug-resistant tuberculosisen_ZA
dc.subject.otherCo-infectionsen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherDrug therapyen_ZA
dc.subject.otherMeta-analysisen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.titleRisk Factors for Acquired Rifamycin and Isoniazid resistance: A systematic review and meta-analysisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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