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Discordance between genotypic resistance and pseudovirus phenotypic resistance in AIDS patients after long‐term antiretroviral therapy and virological failure
Author(s) -
Yang Jing,
Geng Wenqing,
Zhang Min,
Han Xiaoxu,
Shang Hong
Publication year - 2014
Publication title -
journal of basic microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.58
H-Index - 54
eISSN - 1521-4028
pISSN - 0233-111X
DOI - 10.1002/jobm.201300415
Subject(s) - virology , biology , genotype , drug resistance , genotyping , phenotype , zidovudine , lamivudine , lentivirus , reverse transcriptase , genetics , virus , gene , viral disease , polymerase chain reaction , hepatitis b virus
Sixteen original recombinant pseudoviruses were generated by cloning the reverse transcriptase and protease genes of human immunodeficiency virus (HIV)‐1 from patients into a plasmid vector (pNL4‐3‐ΔE‐EGFP). By site‐directed mutagenesis two restriction endonuclease sites, Apa I and Age I, were inserted into pNL4‐3‐ΔE‐EGFP. Phenotypic susceptibility of recombinant pseudoviruses to five different classes of antiretroviral drugs was determined using a luciferase reporter assay system. The results were subjected to comparative analyses to detect genotype–phenotype associations. Among 16 strains tested, 12 strains had a discordant genotype–phenotype resistance pattern to at least one drug. In five strains resistance to two, in two strains to three, and in one strain resistance to four drugs was detected. HIV resistance genotyping could predict the phenotype for nevirapine and azidothymidine. For lamivudine, 2′‐3′‐didehydro‐2′‐3′dideoxythymidine and didanosine, phenotypic resistance testing was necessary. The study showed that in patients who experienced long‐term highly active antiretroviral therapy and virological failure, there is some discordance between genotypic and phenotypic HIV drug resistance. To address the issue of limited resources in China, genotypic and phenotypic resistance testing should be done for different drugs in order to guide clinical therapy more effectively.