Antiretroviral Switch Studies for Metabolic Complications

• SWATCH Study: A Multicenter Trial of Proactive Treatment Switching. Results at Nine Months of Follow-Up. (Poster 669)
  Authored by E. Negredo, J. Martinez-Picado, L. Ruiz, C. Zala, K. Hertogs, C. Boucher, R. D'Aquila, B. Clotet, and The Swatch Study Team
  View the original abstract

Would a practice of proactively switching antiretrovirals before virologic failure produce a more durable response? The rationale behind such a strategy is that one could preempt virologic rebound, and hence reduce accumulating drug resistance. This novel study -- called "SWATCH" for "Switching Antiretroviral Therapy Combinations against HIV" -- examined the strategy of regular cycling of therapy compared with continuous treatment with two standard regimens.

Patients were eligible if they were antiretroviral therapy-naive and had a baseline viral load >5,000 copies/ml. At enrollment, they were assigned to one of three treatment arms:

1. d4T/ddI/efavirenz

2. AZT/3TC/nelfinavir

3. successive 3-month cycles of these two regimens

At one year of follow-up, there was no significant difference between the three arms based on intention-to-treat analysis (approximately 70%, 70%, and 80% being <400 for the efavirenz, nelfinavir, and switch groups respectively). However, when the results were examined solely on the basis of virologic failure, the switch group was significantly better than the other two, with no virologic failures occurring in this group versus seven and three in the efavirenz and nelfinavir arms. No differences were seen in CD4 responses. Quality of life measures were best for the efavirenz group, as there was a high rate of complaints due to nelfinavir-related diarrhea. The study is ongoing, and the investigators plan to do genotypic analysis of HIV co-cultured from peripheral blood mononuclear cells to see if there is differing evolution in resistance even among those who have a suppressed viral load.

Although the results of this study show a potential benefit of proactive switching, adaptation of this strategy now for clinical practice would be premature. The improved results in the switching group could have resulted from pre-empting resistance, but an alternative explanation could be that they received a wider variety of active agents -- and all three drug classes -- during the same treatment interval. It will be interesting to see further follow-up of this study as it progresses.