B Gröschel, N Himmel, J Cinatl, C Périgaud, G Gosselin, J L Imbach, H W Doerr, J Cinatl
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ddC- and 3TC-bis(SATE) monophosphate prodrugs overcome cellular resistance mechanisms to HIV-1 associated with cytidine kinase deficiency.
A 2',3'-dideoxycytidine (ddC)-resistant T-lymphoid cell line (MOLT-4/8rddC250), in which deoxycytidine kinase (dCK) gene-expression was decreased when compared with parental cells, has been selected. Cytotoxic and antiretroviral activity of ddC and 3TC was significantly lower in MOLT-4/8rddC250-than in parental MOLT-4/8 cells. ddC- and 3TC-bis(SATE)phosphotriesters completely overcame cellular resistance mechanisms and showed comparable both cytotoxic and antiretroviral activity in parental and ddC-resistant cells.
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