• Viral Resistance Results from the International, Multicenter, Randomized, Placebo-Controlled, 48-Week Study of Hydroxyurea (HU) or Placebo Combined with Efavirenz (EFV), Didanosine (ddl) and Stavudine (d4T) in Treatment-Naive and -Experienced Patients (Poster 445)
  Authored by V. Johnson, C. Delaugerre, J. Hazelwood, B. Berzins, E. Belsey, R. Rhodes, V. Calvez, C. Katlama, and R. Murphy for the Intl. 3d Study Team
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Last year, a study of the combination of d4T, ddI, and Sustiva was presented. This study also tested the benefits of adding hydroxyurea (HU) to the combination given the information suggesting increased potency from the ddI when adding this agent. This regimen was given to those who were antiviral-naive as well as those who were already on their first regimen, and switched to this as a second regimen. The results showed that for those who were antiviral-naive, there was no added benefit to the HU, and both arms had high degrees of suppression. Further there was added side effects from the HU, leading to the now widespread conclusion that HU has no role in an initial regimen. However, the results did show a trend favoring a higher likelihood of suppression in experienced persons when adding HU, with 80% on HU, and 57% off HU achieving a viral load <50 copies.

This presentation reported on the patterns of resistance in those who did not maintain suppression. Not surprisingly, the main finding is that there was resistance seen to the non-nucleoside Sustiva in those who rebounded. In addition, those who were nucleoside experienced prior to entry sometimes would rebound with viral strains showing resistance to the nucleoside agents. The addition of HU had no clear impact on the patterns of resistance if it did occur.

Overall, these results fit in with what can be expected in resistance patterns. It has been noted that resistance can more readily occur with some agents more than others. Here, the results support that resistance can be more readily seen to a non-nucleoside than to either of these two nucleoside antivirals. However, preexisting resistance does not fade away when switching agents, and patterns of resistance on a regimen reflect not only the current medications, but will also represent the cumulative resistance from other medications taken in the past. Avoiding resistance to any regimen remains the goal whenever antivirals are used.