Selection of a T-Cell Line Resistant to Stavudine and Zidovudine by Prolonged Treatment with Stavudine

Abstract
It has been demonstrated that prolonged treatment with nucleoside analogues, such as 3′-azido-3′-deoxythymi-dine (zidovudine), 2’,3′-dideoxycytidine (zalcitabine) and 9-(2-phosphonylmethoxyethyl) adenine (PMEA), may cause selection of cells that are resistant to their anti-HIV activity. A human T-lymphoblastoid cell line that is resistant to the antiviral and cytotoxic activity of 2’,3′-didehydro-3′-deoxythymidine (stavudine) has developed as a result of prolonged treatment. These cells, called CEMstavudine, are also less sensitive to zidovudine. The cellular/pharmacological resistance acquired by the CEMstavudine cells is relatively low and appears to correlate with a reduction in thymidine kinase (TK) activity, rather than with a decreased expression of TK mRNA.