دورية أكاديمية

A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort.

التفاصيل البيبلوغرافية
العنوان: A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort.
المؤلفون: Telele, Nigus Fikrie, Kalu, Amare Worku, Gebre-Selassie, Solomon, Fekade, Daniel, Marrone, Gaetano, Grossmann, Sebastian, Neogi, Ujjwal, Tegbaru, Belete, Sönnerborg, Anders
المصدر: BMC Infectious Diseases; 7/1/2019, Vol. 19 Issue 1, pN.PAG-N.PAG, 1p, 1 Black and White Photograph, 1 Diagram, 3 Charts
مصطلحات موضوعية: VIRAL genomes, REVERSE transcriptase, HIV, DRUG resistance, HUMAN beings in art
مصطلحات جغرافية: ETHIOPIA
مستخلص: Background: Antiretroviral therapy (ART) was rolled-out in Ethiopia in 2005, but there are no reports on outcome of ART and human immunodeficiency virus drug resistance (HIVDR) at national level. We described acquired drug resistance mutations in pol gene and performed a viral genome wide association study in virologic treatment failure patients who started first line ART during 2009-2011 in the first large countrywide HIV cohort in Ethiopia.Methods: The outcome of tenofovir (TDF)- and zidovudine (ZDV)-based ART was defined in 874 ART naïve patients using the on-treatment (OT) and intention-to-treat (ITT) analyses. Genotypic resistance testing was done in patients failing ART (> 1000 copies/ml) at month 6 and 12. Near full-length genome sequencing (NFLG) was used to assess amino acid changes in HIV-1 gag, pol, vif, vpr, tat, vpu, and nef genes between paired baseline and month 6 samples.Results: High failure rates were found in ITT analysis at month 6 and 12 (23.3%; 33.9% respectively). Major nucleoside and non-nucleoside reverse transcriptase (NRTI/NNRTI) drug resistance mutations were detected in most failure patients at month 6 (36/47; 77%) and month 12 (20/30; 67%). A high rate of K65R was identified only in TDF treated patients (35.7%; 50.0%, respectively). No significant difference was found in failure rate or extent of HIVDR between TDF- and ZDV- treated patients. All target regions of interest for HIVDR were described by NFLG in 16 patients tested before initiation of ART and at month 6.Conclusion: In this first Ethiopian national cohort, a high degree of HIVDR was seen among ART failure patients, independent on whether TDF- or ZDV was given. However, the major reason to ART failure was lost-to-follow-up rather than virologic failure. Our NFLG assay covered all relevant target genes for antiretrovirals and is an attractive alternative for HIVDR surveillance. [ABSTRACT FROM AUTHOR]
Copyright of BMC Infectious Diseases is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
قاعدة البيانات: Complementary Index
الوصف
تدمد:14712334
DOI:10.1186/s12879-019-4196-8