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HIV-1C proviral DNA for detection of drug resistance mutations
- Source :
- PLoS ONE, Vol 13, Iss 11, p e0207079 (2018), PLoS ONE
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- Background Using HIV proviral DNA as a template may be suitable for initial detection of transmitted drug resistance mutations (TDRMs) as it is easy to handle and less expensive compared to RNA. However, existing literatures which are mainly focused on HIV-1B subtypes DNA extracted from PBMCs revealed controversial findings ranging from the detection of significantly lower or higher mutations in proviral DNA compared to historic viral RNA. Thus, to verify whether viral RNA or proviral DNA has improved sensitivity in detecting transmitted genotypic drug resistance mutations paired viral RNA and proviral DNA (which is directly extracted from stored whole blood) samples were tested from Ethiopian antiretroviral naive HIV-1C infected subjects. Methods In the present comparative study the frequency of TDR mutations was assessed in paired samples of viral RNA and proviral DNA (extracted directly from stored whole blood) of HIV-1C infected treatment naïve patients and interpreted using the 2009 WHO drug resistance surveillance mutation lists, Stanford University drug resistance data base and International Antiviral Society-USA mutation lists. Results High agreement in rate of TDR between the two compartments was observed using the WHO mutation lists. While mutations G190A and E138A were concurrently found in both compartments, others such as G73S on PR and A62V, M184I, M230I on RT were identified in proviral DNA only. All signature mutations seen in viral RNA were not missed in proviral DNA. Conclusions The concordance of major genotype drug resistance mutation between RNA and proviral DNA in treatment naïve patients suggests that proviral DNA might be an alternative approaches for an initial assessment of drug resistance prior to initiation of antiretroviral therapy using the WHO mutations lists in resource-limited countries. However, the clinical importance of TDRMs observed only in proviral DNA in terms of being a risk factor for virologic failure and whether they limit future treatment options needs additional investigation using more sensitive sequencing approaches such as Next Generation Sequencing (NGS).
- Subjects :
- RNA viruses
Male
Molecular biology
Gene Identification and Analysis
Human immunodeficiency virus (HIV)
lcsh:Medicine
HIV Infections
Proviral dna
Drug resistance
Pathology and Laboratory Medicine
medicine.disease_cause
Database and Informatics Methods
Sequencing techniques
Immunodeficiency Viruses
Proviruses
Medicine and Health Sciences
Medicine
lcsh:Science
Phylogeny
Multidisciplinary
Microbial Mutation
RNA sequencing
Middle Aged
Medical Microbiology
Viral Pathogens
Viruses
RNA, Viral
Female
Pathogens
Research Article
Adult
Anti-HIV Agents
Microbiology
Young Adult
Extraction techniques
Antibiotic resistance
Microbial Control
Retroviruses
Drug Resistance, Viral
Genetics
Humans
Mutation detection
Mutation Detection
Microbial Pathogens
Pharmacology
Polymorphism, Genetic
business.industry
Lentivirus
lcsh:R
Organisms
Biology and Life Sciences
HIV
Correction
Sequence Analysis, DNA
Virology
RNA extraction
Research and analysis methods
Biological Databases
Molecular biology techniques
Mutation Databases
DNA, Viral
Mutation
HIV-1
Leukocytes, Mononuclear
lcsh:Q
Antimicrobial Resistance
business
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....2a2a9bc5d2850e26f2ab883ac76807e6