We are developing a protocol for NRTI sequencing in our practice. Unfortunately, we do not routinely have access to genotypic testing. Neither abacavir nor didanosine is a good choice in our setting as first line drugs for various reasons. We are considering d4T/3TC as the initial nuke component, followed by AZT/ddI. What are your thoughts on this sequence in terms of the resistance implications?
Dr. Mark Wainberg responds:
There is no problem with using d4T/3TC as an initial nucleoside combination. However, in the event that this regimen fails, it is not necessarily recommended that AZT/ddI be used in its place. Indeed, this is a classic example in which genotypic testing may prove essential as a guide to follow-up therapy. For example, should d4T lead to any of a number of thymidine-associated mutations (TAMs) at positions 41, 67, 70, 215, etc, it is doubtful that AZT could be used in a subsequent regimen because of cross resistance with d4T. In contrast, there would be little problem associated with ddI as a follow-up. You might consider maintaining the 3TC while adding ddI. You might also consider the use of an NNRTI together with ddI in the event of initial failure.
