What is the latest information on using d4T following AZT failure?
Dr. Mark Wainberg responds:
Most cross-resistance data describe the extent to which isolates from patients receiving other treatments are resistant to d4T. Most of these data show that patients who have received prior AZT therapy have a markedly diminished response to treatment with d4T either alone or in combination with other drugs. There are few data available on patients who have switched from d4T to AZT.
The notion that AZT and d4T are cross-resistant is strengthened by the observation that the most common mutations in patients receiving d4T include the AZT-resistance mutations M41L and T215Y. Other potential mechanisms of cross-resistance between d4T and other drugs include multinucleoside resistance mediated by Q151M and the b3-b4 insertion (see AZT resistance summary). In addition, recombinant reverse transcriptase that contains AZT-associated mutations, i.e. thymidine-associated mutations, or TAMs, display diminished sensitivity to d4T triphosphate, the active form of d4T.
