Antiretroviral Chemotherapy I

• Successful Substitution of Protease Inhibitors with Efavirenz (EFV) in Patients with Undetectable Viral Loads -- A Prospective, Randomized, Multicenter, Open-Label Study (DMP 049) (Slide Session 20)
  Authored by S. Becker, A. Rachlis, J. Gill, E. Dejesus, G. Pierone, L. Kirkland, S. Koosian, D. Farina, D. Labriola, N. Ruiz, L. Bessen, and S. Villano
  View the original abstract

For those now on a combination of two nucleosides and either one or two protease inhibitors, there have been studies aimed at substituting a different medication for the protease inhibitors. Much of the work has gone into studies using a non-nucleoside instead of a protease inhibitor, as there are different potential side effects seen in these two classes of antivirals. This report was the final data set, first seen at the ICAAC meeting in 2000, which substituted efavirenz for the protease inhibitor(s) in the combination.

Persons were eligible if they were on their first protease inhibitor combination. Some had dual-nucleoside use before adding the protease inhibitor, and this was allowed only if there was a documented viral load below 400 to 500 copies while on the nucleoside-only combination. Participants were randomized to receive either efavirenz or stay on their current protease inhibitor. Baseline characteristics of those in this study of the 346 enrolled include a CD4 count of about 550, and about 20 months of prior protease inhibitor use. Indinavir was used in 44%, while 30% were on nelfinavir. About 12% were on a dual protease inhibitor combination. All had a viral load of less than 50 copies to enter this study.

When looking at the data for those who stayed on their regimen, the success rate of maintaining a viral load of less than 50 copies was 96% for efavirenz, versus 90% for those on their protease inhibitor, which was significant (p=.024). When looking at the overall group in an intent-to-treat analysis, the results still favored efavirenz, with 84% vs. 73% maintaining suppression over time. There were no differences in CD4 counts in these two groups. There were minimal changes in the lipid profiles in this study in the two arms, although there was a small average rise in the HDL cholesterol in the group who switched to efavirenz.

Why might this result have occurred? One additional observation from the study suggests that efavirenz was also associated with better adherence. About half as many participants reported missing a dose of efavirenz versus the protease inhibitor they were on, and this was true whether looking at those who missed one dose, or multiple doses over time.

These results confirm the previous presentations of these data, suggesting that those now on a protease inhibitor and doing well, might do just as well, or even better, when switching to an alternative agent. It may be that simplifying the regimen in any way, including pharmacokinetic adjustments to the protease inhibitors may be similarly associated with improved suppression rates, since simpler regimens have generally done better overall. And it is reasonable to note that both arms did well in this study. Nonetheless, this study adds yet more data supporting the role of the non-nucleosides in current treatment strategies.