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

BMC Infectious Diseases

Daniel Fekade¹  Solomon Gebre-Selassie²  Gaetano Marrone³  Anders Sönnerborg⁴  Nigus Fikrie Telele⁴  Amare Worku Kalu⁴  Ujjwal Neogi⁴  Sebastian Grossmann⁴  Belete Tegbaru⁵ 

[1] Department of Medicine, Addis Ababa University;Department of Microbiology, Immunology and Parasitology, Addis Ababa University;Department of Public Health Sciences, Karolinska Institutet;Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital;Ethiopian Public Health Institute;

关键词: HIV-1 drug resistance;    Near-full length genome;    Genome wide association;    Antiretroviral therapy;    Countrywide HIV cohort;    Ethiopia;   

DOI  :  10.1186/s12879-019-4196-8

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown