Time (again) for a Randomized Trial of Pharmacogenetics of Antiretroviral Therapy

Abstract

Last year, I managed to attain funding for the same grant rejected by several agencies. The reason was clearly stated: it is premature to run a pharmacogenetics-driven randomized trial on the basis of current knowledge on the genetics of toxicity to a number of antiretroviral agents, and it is too expensive. This reasonable rejection should not lead to questioning the research goals in the field: the identification of genetic markers, their association with an intermediate phenotype (the immediate biological effect of a variant gene, for example, an increase in unconjugated bilirubin), and the final correla tion with a clinical end point – such as severe toxicity, or treatment discontinuation. A clinical trial should formalize the ana lysis and provide the basis for translating it into medical economic terms: the cost–effectiveness of a new test. Let’s go down this list.