Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study

Summary: Background: South Africa has a high burden of rifampicin-resistant tuberculosis (including multidrug-resistant [MDR] tuberculosis), with increasing rifampicin-monoresistant (RMR) tuberculosis over time. Resistance acquisition during first-line tuberculosis treatment could be a key contribu...

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Autores principales:	Helen Cox, ProfPhD, Zubeida Salaam-Dreyer, PhD, Galo A Goig, PhD, Mark P Nicol, ProfPhD, Fabrizio Menardo, PhD, Anzaan Dippenaar, PhD, Erika Mohr-Holland, MPH, Johnny Daniels, BA, Patrick G T Cudahy, PhD, Sonia Borrell, PhD, Miriam Reinhard, MD, Anna Doetsch, MSc, Christian Beisel, PhD, Anja Reuter, MD, Jennifer Furin, MD, Sebastien Gagneux, ProfPhD, Robin M Warren, ProfPhD
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Medicine (General) R5-920 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/eabc95b2fba449618f5b7dcb2a25c8ac
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spelling	oai:doaj.org-article:eabc95b2fba449618f5b7dcb2a25c8ac2021-11-04T04:40:42ZPotential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study2666-524710.1016/S2666-5247(21)00144-0https://doaj.org/article/eabc95b2fba449618f5b7dcb2a25c8ac2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666524721001440https://doaj.org/toc/2666-5247Summary: Background: South Africa has a high burden of rifampicin-resistant tuberculosis (including multidrug-resistant [MDR] tuberculosis), with increasing rifampicin-monoresistant (RMR) tuberculosis over time. Resistance acquisition during first-line tuberculosis treatment could be a key contributor to this burden, and HIV might increase the risk of acquiring rifampicin resistance. We assessed whether HIV during previous treatment was associated with RMR tuberculosis and resistance acquisition among a retrospective cohort of patients with MDR or rifampicin-resistant tuberculosis. Methods: In this retrospective cohort study, we included all patients routinely diagnosed with MDR or rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa, between Jan 1, 2008, and Dec 31, 2017. Patient-level data were obtained from a prospective database, complemented by data on previous tuberculosis treatment and HIV from a provincial health data exchange. Stored MDR or rifampicin-resistant tuberculosis isolates from patients underwent whole-genome sequencing (WGS). WGS data were used to infer resistance acquisition versus transmission, by identifying genomically unique isolates (single nucleotide polymorphism threshold of five). Logistic regression analyses were used to assess factors associated with RMR tuberculosis and genomic uniqueness. Findings: The cohort included 2041 patients diagnosed with MDR or rifampicin-resistant tuberculosis between Jan 1, 2008, and Dec 31, 2017; of those, 463 (22·7%) with RMR tuberculosis and 1354 (66·3%) with previous tuberculosis treatment. In previously treated patients, HIV positivity during previous tuberculosis treatment versus HIV negativity (adjusted odds ratio [OR] 2·07, 95% CI 1·35–3·18), and three or more previous tuberculosis treatment episodes versus one (1·96, 1·21–3·17) were associated with RMR tuberculosis. WGS data showing MDR or rifampicin-resistant tuberculosis were available for 1169 patients; 360 (30·8%) isolates were identified as unique. In previously treated patients, RMR tuberculosis versus MDR tuberculosis (adjusted OR 4·96, 3·40–7·23), HIV positivity during previous tuberculosis treatment (1·71, 1·03–2·84), and diagnosis in 2013–17 (1·42, 1·02–1·99) versus 2008–12, were associated with uniqueness. In previously treated patients with RMR tuberculosis, HIV positivity during previous treatment (adjusted OR 5·13, 1·61–16·32) was associated with uniqueness as was female sex (2·50 [1·18–5·26]). Interpretation: These data suggest that HIV contributes to rifampicin-resistance acquisition during first-line tuberculosis treatment and that this might be driving increasing RMR tuberculosis over time. Large-scale prospective cohort studies are required to further quantify this risk. Funding: Swiss National Science Foundation, South African National Research Foundation, and Wellcome Trust.Helen Cox, ProfPhDZubeida Salaam-Dreyer, PhDGalo A Goig, PhDMark P Nicol, ProfPhDFabrizio Menardo, PhDAnzaan Dippenaar, PhDErika Mohr-Holland, MPHJohnny Daniels, BAPatrick G T Cudahy, PhDSonia Borrell, PhDMiriam Reinhard, MDAnna Doetsch, MScChristian Beisel, PhDAnja Reuter, MDJennifer Furin, MDSebastien Gagneux, ProfPhDRobin M Warren, ProfPhDElsevierarticleMedicine (General)R5-920MicrobiologyQR1-502ENThe Lancet Microbe, Vol 2, Iss 11, Pp e584-e593 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920 Microbiology QR1-502
spellingShingle	Medicine (General) R5-920 Microbiology QR1-502 Helen Cox, ProfPhD Zubeida Salaam-Dreyer, PhD Galo A Goig, PhD Mark P Nicol, ProfPhD Fabrizio Menardo, PhD Anzaan Dippenaar, PhD Erika Mohr-Holland, MPH Johnny Daniels, BA Patrick G T Cudahy, PhD Sonia Borrell, PhD Miriam Reinhard, MD Anna Doetsch, MSc Christian Beisel, PhD Anja Reuter, MD Jennifer Furin, MD Sebastien Gagneux, ProfPhD Robin M Warren, ProfPhD Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study
description	Summary: Background: South Africa has a high burden of rifampicin-resistant tuberculosis (including multidrug-resistant [MDR] tuberculosis), with increasing rifampicin-monoresistant (RMR) tuberculosis over time. Resistance acquisition during first-line tuberculosis treatment could be a key contributor to this burden, and HIV might increase the risk of acquiring rifampicin resistance. We assessed whether HIV during previous treatment was associated with RMR tuberculosis and resistance acquisition among a retrospective cohort of patients with MDR or rifampicin-resistant tuberculosis. Methods: In this retrospective cohort study, we included all patients routinely diagnosed with MDR or rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa, between Jan 1, 2008, and Dec 31, 2017. Patient-level data were obtained from a prospective database, complemented by data on previous tuberculosis treatment and HIV from a provincial health data exchange. Stored MDR or rifampicin-resistant tuberculosis isolates from patients underwent whole-genome sequencing (WGS). WGS data were used to infer resistance acquisition versus transmission, by identifying genomically unique isolates (single nucleotide polymorphism threshold of five). Logistic regression analyses were used to assess factors associated with RMR tuberculosis and genomic uniqueness. Findings: The cohort included 2041 patients diagnosed with MDR or rifampicin-resistant tuberculosis between Jan 1, 2008, and Dec 31, 2017; of those, 463 (22·7%) with RMR tuberculosis and 1354 (66·3%) with previous tuberculosis treatment. In previously treated patients, HIV positivity during previous tuberculosis treatment versus HIV negativity (adjusted odds ratio [OR] 2·07, 95% CI 1·35–3·18), and three or more previous tuberculosis treatment episodes versus one (1·96, 1·21–3·17) were associated with RMR tuberculosis. WGS data showing MDR or rifampicin-resistant tuberculosis were available for 1169 patients; 360 (30·8%) isolates were identified as unique. In previously treated patients, RMR tuberculosis versus MDR tuberculosis (adjusted OR 4·96, 3·40–7·23), HIV positivity during previous tuberculosis treatment (1·71, 1·03–2·84), and diagnosis in 2013–17 (1·42, 1·02–1·99) versus 2008–12, were associated with uniqueness. In previously treated patients with RMR tuberculosis, HIV positivity during previous treatment (adjusted OR 5·13, 1·61–16·32) was associated with uniqueness as was female sex (2·50 [1·18–5·26]). Interpretation: These data suggest that HIV contributes to rifampicin-resistance acquisition during first-line tuberculosis treatment and that this might be driving increasing RMR tuberculosis over time. Large-scale prospective cohort studies are required to further quantify this risk. Funding: Swiss National Science Foundation, South African National Research Foundation, and Wellcome Trust.
format	article
author	Helen Cox, ProfPhD Zubeida Salaam-Dreyer, PhD Galo A Goig, PhD Mark P Nicol, ProfPhD Fabrizio Menardo, PhD Anzaan Dippenaar, PhD Erika Mohr-Holland, MPH Johnny Daniels, BA Patrick G T Cudahy, PhD Sonia Borrell, PhD Miriam Reinhard, MD Anna Doetsch, MSc Christian Beisel, PhD Anja Reuter, MD Jennifer Furin, MD Sebastien Gagneux, ProfPhD Robin M Warren, ProfPhD
author_facet	Helen Cox, ProfPhD Zubeida Salaam-Dreyer, PhD Galo A Goig, PhD Mark P Nicol, ProfPhD Fabrizio Menardo, PhD Anzaan Dippenaar, PhD Erika Mohr-Holland, MPH Johnny Daniels, BA Patrick G T Cudahy, PhD Sonia Borrell, PhD Miriam Reinhard, MD Anna Doetsch, MSc Christian Beisel, PhD Anja Reuter, MD Jennifer Furin, MD Sebastien Gagneux, ProfPhD Robin M Warren, ProfPhD
author_sort	Helen Cox, ProfPhD
title	Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study
title_short	Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study
title_full	Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study
title_fullStr	Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study
title_full_unstemmed	Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study
title_sort	potential contribution of hiv during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in south africa: a retrospective molecular epidemiology study
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/eabc95b2fba449618f5b7dcb2a25c8ac
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Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study

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