Decreased anti-human immunodeficiency virus type-1 activities of 2',3'-dideoxynucleoside analogs in MOLT-4 cell sublines resistant to 2',3'-dideoxynucleoside analogs.
Human T-lymphoid MOLT-4 cells were grown continuously for more than 1 year in medium containing either 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxycytidine (ddC) at concentrations similar to peak plasma levels found in clinical trials in patients with AIDS. To test antiviral activities of the nucleoside analogs against HIV-1 in the cell sublines designated MOLT-4r-AZT, MOLT-4r-ddI and MOLT-4r-ddC, the number of infected cells, p24 HIV-1 antigen in culture medium and syncytium formation of infected cultures were determined. The results showed that anti-HIV-1 activities of AZT, ddI and ddC were significantly decreased in the resistant MOLT-4 cell sublines grown continuously with the respective nucleoside analog, probably due to the development of cell populations resistant to the drugs.
Cinatl
J
J
Department of Medical Virology, J. W. Goethe University, Frankfurt, Federal Republic of Germany.
Cinatl
J
J
Weber
B
B
Rabenau
H
H
Weissflog
A
A
Mainke
M
M
Kornhuber
B
B
Doerr
H W
HW
D002460:Cell Line; D003470:Culture Media; D016049:Didanosine / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D013997:Time Factors; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D003470:Culture Media; D015224:Dideoxynucleosides; D016655:HIV Core Protein p24; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine