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

Autor: Belete Tegbaru, Gaetano Marrone, Sebastian Grossmann, Solomon Gebre-Selassie, Anders Sönnerborg, Daniel Fekade, Amare Worku Kalu, Ujjwal Neogi, Nigus Fikrie Telele
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Genotype
Anti-HIV Agents
030106 microbiology
HIV Infections
Genome-wide association study
HIV Integrase
Drug resistance
lcsh:Infectious and parasitic diseases
Cohort Studies
Near-full length genome
03 medical and health sciences
Zidovudine
0302 clinical medicine
Medical microbiology
Internal medicine
Drug Resistance
Viral
medicine
Humans
lcsh:RC109-216
Treatment Failure
030212 general & internal medicine
Tenofovir
business.industry
virus diseases
Countrywide HIV cohort
Antiretroviral therapy
Reverse transcriptase
3. Good health
Infectious Diseases
Parasitology
Mutation
Cohort
HIV-1
Genome wide association
Reverse Transcriptase Inhibitors
Female
Ethiopia
business
HIV-1 drug resistance
Research Article
Genome-Wide Association Study
medicine.drug
Zdroj: BMC Infectious Diseases, Vol 19, Iss 1, Pp 1-10 (2019)
BMC Infectious Diseases
ISSN: 1471-2334
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12879-019-4196-8) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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