Frequency of mutations conferring resistance to nucleoside reverse transcriptase inhibitors in human immunodeficiency virus type 1-infected patients in Korea.
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.
Cho
Young Keol
YK
Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea. ykcho2@amc.seoul.kr
Sung
Heungsup
H
Ahn
Sun Hee
SH
Bae
In Gyu
IG
Woo
Jun Hee
JH
Won
Young Ho
YH
Kim
Dae Ghon
DG
Kang
Moon Won
MW
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
D019380:Anti-HIV Agents; D028321:Plant Preparations; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase