The evaluation of metabolic function and fat redistribution in clinical trials.

Changes in lipid and carbohydrate metabolism and in body composition associated with the most potent and effective therapies available are being reported with increasing frequency. These changes could potentially lead to increased risks of cardiovascular disease. Clinical trials set up to investigate new antiretroviral therapies need to explore the therapies' impact on these potentially serious adverse outcomes, at least in a subset of patients. The measurements that are feasible to include for all patients clearly differ from those required by a metabolic substudy. We propose the following: firstly, a minimal set of parameters that should be included in all trials; secondly, a desirable set of parameters that should be included whenever possible; and thirdly, a list of exploratory measures that should be considered. These exploratory measures are classified by the different mechanisms for changes in body composition or weight: endocrinal, cardiovascular, sterol and chemokine/cytokine pathways. Standardized instruments for evaluating patients' reports of body changes and potential methods for assessing the risk of cardiovascular disease are described. Minimum and desirable standards for methods of measurement are also proposed. The choice of parameters is based on expert clinical opinion. The experts consulted include investigators from four large ongoing clinical trials with substudies specifically designed to investigate lipid and carbohydrate metabolism and changes in body composition, together with standard parameters for measurement within individual mechanistic pathways. The parameters proposed should be kept under review as the body of knowledge about metabolic function and fat redistribution in HIV infection increases.