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인면역결핍바이러스감염에서 Ribavirin의 Lamivudine에 대한 길항효과

Other Titles
 Antagonistic effect of Ribavirin on Lamivudine against HIV-1 infection 
Authors
 허애정  ;  남정구  ;  장경희  ;  염준섭  ;  최준용  ;  송영구  ;  김성순 
Citation
 Journal of the Korean Society for Chemotherapy (대한화학요법학회지), Vol.20(1) : 35-47, 2002 
Journal Title
 Journal of the Korean Society for Chemotherapy (대한화학요법학회지) 
ISSN
 1225-7850 
Issue Date
2002
Keywords
HIV ; HCV ; Lamivudine(3-TC) ; Ribavirin(RBV) ; drug ineraction
Abstract
Background : One of the main concerns of interferon/ribavirin(RBV) treatment in Human immunodeficiency virus(HIV)/Hepatitis C virus(HCV) coinfected patients is that of drug-drug interactions. Recent studies reveal that RBV is antagonistic with zidovudine(ZDV), stavudine(d4T) and synergistic with didanosine(ddI). The phosphorylation of lamivudine(3TC) utilizes the enzyme deoxycytidine kinase. Manipulation of 3TC phosphorylation is a possible therapeutic strategy for modulating antiretroviral efficacy and cvtotoxicity of 3TC. Methods : MT-4 cell lines were maintained in RPW 1640 growth medium as a cell suspension(1.96 x 106cells/ml), doubling approximately every 48-72 hr. Cells were incubated with ZDV(0.0001-1000mM) and 3TC(0.00001- l OOmM) in the. presence and absence of RBV(2,uM) in 96-well microtiter plates and cytotoxicity was determined using modified MTT assay. At the end of the 7 days, the cell-free supernatant was serially diluted and samples(100 /-LL) were then assayed for p24 antigen with ELISA to evaluate the inhibitory effect on HIV-1 replication. The results were expressed in terms of the 50% inhibitory concentration(IC50). Analysis was done by Wilcoxon rank sum test. Results : 3TC alone significantly reduced p24 antigen production, with an IC50 0.067mM and addition of RBV increased -the IC50 approximately 8.4 fold (0.563mM). However, at higher concentration of 3TC, the antagonistc effect of RBV was lost. The decrease in the cytotoxic and antiviral efficacy of ZDV in the presence of RBV is consistent with previous studies that have demonstrated reduced ZDV activation. Conclusion : The addition of RBV siginificantly reduced cytotoxicity and antiretroviral efficacy of 3TC in MT-4 cell lines and the antagonistic effect of RBV is concentration dependent. This study provides further insight into the complex interaction between RBV and 3TC in vitro.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, June Myung(김준명)
Song, Young Goo(송영구) ORCID logo https://orcid.org/0000-0002-0733-4156
Choi, Jun Yong(최준용) ORCID logo https://orcid.org/0000-0002-2775-3315
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143369
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