Kalil and colleagues' meta-analysis of CMV management trials (1) is an important contribution to the literature that should be widely cited. The goal of my editorial was not to rephrase or critique their article, which can stand on its own merits. Rather, I hoped to communicate some historical perspective on the topic and discuss the current controversy between prophylactic and preemptive approaches to the management of CMV infection.

One concern I had was that some readers might see CMV prophylaxis as the better overall strategy, because the meta-analysis found more benefits for this management strategy than for preemptive therapy. I wanted to issue a caveat against drawing this sort of conclusion. In order to strengthen that caveat, I extracted and analyzed data from Kalil and colleagues' article that, in fact, showed that their preemptive and prophylactic populations were quantitatively and qualitatively different. I believe that this was a valid and legitimate exercise and that it supported my claim that no reliable conclusion could be drawn from the data favoring either approach to CMV management.

I stand by my statement that all of the large (>100 patients) placebo-controlled trials cited in the study were studies of prophylaxis. The trial by Hibberd and colleagues (2) was randomized and contained more than 100 patients, but it was not placebo-controlled or blinded. It is important to recognize that more resources have been invested in the study of CMV prophylaxis than in preemptive therapy of CMV, and this may have produced a playing field that is not completely flat.

Finally, this letter gives me an opportunity to redress my neglect of acyclovir, whose prophylactic use was shown by the meta-analysis to reduce CMV disease. Acyclovir is clearly less potent than ganciclovir (3) and is never used for preemptive therapy or therapy of established CMV disease, but as Kalil and colleagues have shown, it has proven benefits in the prophylactic setting. Further studies of acyclovir analogues seem warranted. A particularly intriguing regimen to study in high-risk patients would be the combination of valacyclovir prophylaxis and valganciclovir preemptive therapy.