• Virologic Suppression from Different Thymidine Analogue (TA)-Containing HAART Regimen Sequencing Strategies: VIRA 3001 (Poster 444)
  Authored by C. Cohen, N. Graham, M. St. Clair, A. Hirani, and A. Rinehart
  View the original abstract

Last year, the first study documenting the benefits from phenotypic testing was presented at this meeting (VIRA 3001). In this analysis, the focus was comparing the outcome of those who started on either AZT or d4T, and switched to the other drug in the next combination. Because of reports suggesting cross-resistance between these two drugs, it would be expected that little difference would be seen when going in either direction.

This analysis was limited to 99 people who had prior use of AZT but no d4T, and 45 people with prior d4T and no AZT. Overall, as with other similar studies of this type, there were similar patterns of resistance seen in those on either of these two medications. In their next combination, both groups used a non-nucleoside about 45% of the time, and both had similar likelihoods of regimens which combined at least two active antivirals as judged by resistance testing (about 80%).

Despite these similarities in the regimen, there were striking differences seen in the results. There was more success noted in the group who started on AZT and changed to d4T than the reverse order. This result was observed regardless of the degree of resistance seen to either of these two medications at the time of the switch. However, there was more overall success in the regimens of those who had fewer thymidine-associated mutations, supporting other studies that show how difficult it is to suppress viruses containing these mutations, even when using other non-thymidine antivirals in this class.

This study cannot state why this result was observed, and other studies have reported different conclusions about the efficacy of switching from AZT to d4T. Randomized trials are underway to provide a definitive answer to the lingering question concerning whether there are advantages to starting with one versus the other of these medications. Ultimately, the decision for now should be based on maximizing adherence to whichever agent is chosen, and picking the drug for which adherence is more likely, since avoiding resistance by creating a successful regimen remains the preferred strategy.