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 (ddl) or 2', 3'-dideoxycytidine (ddC) at conc entrations similar to peak plasma levels found in clinical trials in p atients with AIDS. To test antiviral activities of the nucleoside anal ogs against HIV-I in the cell sublines designated MOLT-4r-AZT, MOLT-4r -ddl and MOLT-4r-ddC, the number of infected cells, p24 HIV-1 antigen in culture medium and syncytium formation of infected cultures were de termined. The results showed that anti-HIV-1 activities of AZT, ddI an d ddC were significantly decreased in the resistant MOLT-4 cell sublin es grown continuously with the respective nucleoside analog, probably due to the development of cell populations resistant to the drugs.