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.