title: Frequency of mutations conferring resistance to nucleoside reverse transcriptase inhibitors in human immunodeficiency virus type 1-infected patients in Korea.
abstract: A nested PCR and direct sequencing methods were used to define human immunodeficiency virus type 1(HIV-1) reverse transcriptase codons 41 to 219 in DNA from 127 peripheral blood mononuclear cell samples obtained from 35 patients treated with nucleoside reverse transcriptase inhibitors (NRTI). The follow-up period after the initiation of NRTI therapy was 61.8 +/- 31 months (mean and standard deviation). In addition to NRTI therapy, 32 of 35 patients were simultaneously treated with Korean red ginseng. The annual decrease in the CD4(+) T-cell count over 5 years was 13.2/microl. Twenty-eight (80%) of the 35 patients had mutations conferring resistance to NRTI. The frequencies of K70R, T215S/Y/F (i.e., mutation of T at codon 215 to S, Y, or F), D67N/E, K219Q, T69N/S/A, M41L, and L210W mutations conferring resistance to zidovudine were 57.6, 36.4, 36.4, 27.2, 24.2, 21.2, and 12.1%, respectively. Mutations conferring resistance to didanosine and lamivudine were detected in 2 (L74V and M184I; 14.2%) of 11 patients tested and in 4 (M184V; 57%) of 7 patients tested, respectively. In particular, the frequency of T69N/S/A increased sharply after more than 48 months of zidovudine monotherapy. However, Q151M was not detected. As the first report on the frequency of NRTI resistance mutations in Korea, our data suggest that genotypic antiretroviral drug testing should be considered for the design of better drug regimens to improve the management of HIV-1-infected patients.
authors.affiliation: Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea. ykcho2@amc.seoul.kr
authors.forename: Young Keol
authors.initials: YK
authors.lastname: Cho
authors.forename: Heungsup
authors.initials: H
authors.lastname: Sung
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Ahn
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Bae
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Woo
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Won
authors.forename: Dae Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Moon Won
authors.initials: MW
authors.lastname: Kang
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007723:Korea; D008969:Molecular Sequence Data; D009154:Mutation; D005894:Panax; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA
chemical_list: D019380:Anti-HIV Agents; D028321:Plant Preparations; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase