Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing

Abstract Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also n...

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Autores principales:	Nigus Fikrie Telele, Amare Worku Kalu, Solomon Gebre-Selassie, Daniel Fekade, Samir Abdurahman, Gaetano Marrone, Ujjwal Neogi, Belete Tegbaru, Anders Sönnerborg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc42cf948ef74e5b9c1993105737a2b2
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spelling	oai:doaj.org-article:fc42cf948ef74e5b9c1993105737a2b22021-12-02T15:08:37ZPretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing10.1038/s41598-018-25888-62045-2322https://doaj.org/article/fc42cf948ef74e5b9c1993105737a2b22018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25888-6https://doaj.org/toc/2045-2322Abstract Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also next generation sequencing (NGS) was used in a subset of 109 baseline samples of patients. Treatment outcome after 6– and 12–months was assessed by on-treatment (OT) and intention-to-treat (ITT) analyses. Transmitted drug resistance (TDR) was detected in 3.9% (18/461) of successfully sequenced samples by PBSS. However, NGS detected sDRM more often (24%; 26/109) than PBSS (6%; 7/109) (p = 0.0001) and major integrase strand transfer inhibitors (INSTI) DRMs were also found in minor viral variants from five patients. Patients with sDRM had more frequent treatment failure in both OT and ITT analyses. The high rate of TDR by NGS and the identification of preexisting INSTI DRMs in minor wild-type HIV-1 subtype C viral variants infected Ethiopian patients underscores the importance of TDR surveillance in low– and middle–income countries and shows added value of high-throughput NGS in such studies.Nigus Fikrie TeleleAmare Worku KaluSolomon Gebre-SelassieDaniel FekadeSamir AbdurahmanGaetano MarroneUjjwal NeogiBelete TegbaruAnders SönnerborgNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nigus Fikrie Telele Amare Worku Kalu Solomon Gebre-Selassie Daniel Fekade Samir Abdurahman Gaetano Marrone Ujjwal Neogi Belete Tegbaru Anders Sönnerborg Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing
description	Abstract Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also next generation sequencing (NGS) was used in a subset of 109 baseline samples of patients. Treatment outcome after 6– and 12–months was assessed by on-treatment (OT) and intention-to-treat (ITT) analyses. Transmitted drug resistance (TDR) was detected in 3.9% (18/461) of successfully sequenced samples by PBSS. However, NGS detected sDRM more often (24%; 26/109) than PBSS (6%; 7/109) (p = 0.0001) and major integrase strand transfer inhibitors (INSTI) DRMs were also found in minor viral variants from five patients. Patients with sDRM had more frequent treatment failure in both OT and ITT analyses. The high rate of TDR by NGS and the identification of preexisting INSTI DRMs in minor wild-type HIV-1 subtype C viral variants infected Ethiopian patients underscores the importance of TDR surveillance in low– and middle–income countries and shows added value of high-throughput NGS in such studies.
format	article
author	Nigus Fikrie Telele Amare Worku Kalu Solomon Gebre-Selassie Daniel Fekade Samir Abdurahman Gaetano Marrone Ujjwal Neogi Belete Tegbaru Anders Sönnerborg
author_facet	Nigus Fikrie Telele Amare Worku Kalu Solomon Gebre-Selassie Daniel Fekade Samir Abdurahman Gaetano Marrone Ujjwal Neogi Belete Tegbaru Anders Sönnerborg
author_sort	Nigus Fikrie Telele
title	Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing
title_short	Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing
title_full	Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing
title_fullStr	Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing
title_full_unstemmed	Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing
title_sort	pretreatment drug resistance in a large countrywide ethiopian hiv-1c cohort: a comparison of sanger and high-throughput sequencing
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/fc42cf948ef74e5b9c1993105737a2b2
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Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing

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