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An HIV-1 integrase genotype assay for the detection of drug resistance mutations

An HIV-1 integrase genotype assay for the detection of drug resistance mutations Background : The integrase inhibitors (e.g. Raltegravir) are a new class of antiretroviral drugs that have recently become available for the treatment of patients with multi-drug resistant HIV-1 within Australia. The emergence of mutations that confer resistance to the integrase inhibitors has been observed in vivo ; however, no commercial genotyping assay is currently available to screen for resistance to these drugs. Methods : The HIV-1 integrase gene was amplified from plasma-derived HIV-1 viral RNA via reverse transcription-polymerase chain reaction and genotype determined via population DNA sequencing. Drug resistance mutations and polymorphisms were detected using the Stanford University online HIV database. Assay sensitivity and reproducibility were determined using clinical and laboratory-derived samples. Results : Our in-house assay was capable of genotyping the integrase gene from all samples tested ( n = 30) of HIV-1 subtypes B, C, D, F, CFR01_AE and CRF02_AG and can amplify the integrase region from plasma samples containing as few as 50 HIV RNA copies/mL. The assay is highly reproducible (average nucleotide concordance = 99.6%, n = 4) and is capable of detecting resistance-associated mutations. Conclusions : This assay is suitable for routine drug resistance screening of plasma samples from HIV-infected patients receiving integrase inhibitor antiretroviral drugs and also serves as a useful research tool. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Sexual Health CSIRO Publishing

An HIV-1 integrase genotype assay for the detection of drug resistance mutations

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Publisher
CSIRO Publishing
Copyright
CSIRO
ISSN
1448-5028
eISSN
1449-8987
DOI
10.1071/SH09041
pmid
19917199
Publisher site
See Article on Publisher Site

Abstract

Background : The integrase inhibitors (e.g. Raltegravir) are a new class of antiretroviral drugs that have recently become available for the treatment of patients with multi-drug resistant HIV-1 within Australia. The emergence of mutations that confer resistance to the integrase inhibitors has been observed in vivo ; however, no commercial genotyping assay is currently available to screen for resistance to these drugs. Methods : The HIV-1 integrase gene was amplified from plasma-derived HIV-1 viral RNA via reverse transcription-polymerase chain reaction and genotype determined via population DNA sequencing. Drug resistance mutations and polymorphisms were detected using the Stanford University online HIV database. Assay sensitivity and reproducibility were determined using clinical and laboratory-derived samples. Results : Our in-house assay was capable of genotyping the integrase gene from all samples tested ( n = 30) of HIV-1 subtypes B, C, D, F, CFR01_AE and CRF02_AG and can amplify the integrase region from plasma samples containing as few as 50 HIV RNA copies/mL. The assay is highly reproducible (average nucleotide concordance = 99.6%, n = 4) and is capable of detecting resistance-associated mutations. Conclusions : This assay is suitable for routine drug resistance screening of plasma samples from HIV-infected patients receiving integrase inhibitor antiretroviral drugs and also serves as a useful research tool.

Journal

Sexual Health – CSIRO Publishing

Published: Nov 13, 2009

Keywords: HIV drug resistance, HIV integrase genotyping, integrase polymorphism.

References

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