EFFICIENT TRIAL DESIGNS FOR STUDYING COMBINATION ANTIRETROVIRAL TREATMENTS IN PATIENTS WITH VARIOUS RESISTANCE PROFILES

Selecting antiretroviral therapies for human immunodeficiency virus ty pe 1-infected persons is complicated by the availability of a vast num ber of potentially useful drug combinations and by extensive variation among patients in their resistance to various drugs. AIDS clinical tr ials have used designs in which a handful of drug regimens in a few pa tient classes can be compared. Here is proposed implementation of inno vative designs with factorial structure that permit assessment of many treatment arms and patient classes in a single trial; when and how th ey can be appropriately used are discussed. These designs are efficien t, permit systematic investigation of correlations between genetic mut ations and in vivo drug resistance, and provide insight into important drug interactions in people that conventional designs are unable to p rovide. Through creative application of these designs, identification of superior drug combinations and the science of understanding in vivo joint drug dynamics and genotypic resistance will progress at an opti mum pace.