Discussion of “Surrogate Endpoints in AIDS Drug Development: Current Status” by C. Chuang-Stein and R. Demasi

Abstract

This paper is a discussion of “Surrogate Endpoints in AIDS Drug Development: Current Status” by C. Chuang-Stein and R. DeMasi which appears in this issue of the Drug Information Journal. The authors argue that demonstrating HTV-1 RNA reduction and CD4+ cell count increase together constitute operationally acceptable evidence that a treatment would demonstrate a significant clinical benefit if a clinical endpoint trial were carried out. This argument is based primarily on findings from trials of treatments with modest effects. Evidence from recent trials of more potent agents suggest that this concept may not be unreasonable. The issue, however, is not whether this should be done, but rather just how information about viral load reduction and CD4+ cell count increase should be used either to manage patients or to draw conclusions about a drug's likely clinical benefit. In particular, it seems unlikely that finite courses of treatment will be sufficient, and that the effectiveness of a treatment will be defined in terms of its ability to sustain long-term suppression of viral load below levels detectable with sensitive assays.