, Volume 23, Issue 4, pp 201-211
Date: 23 Aug 2012

The ABC of HIV Clinical Trials

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Abstract

There are many different types of HIV clinical trials. For new antiretrovirals, efficacy is established from phase III regulatory trials, which normally include 150–400 patients per treatment arm, studied for 96 weeks. Antiretrovirals used for first-line treatment are usually combined with approved antiretrovirals in triple combinations and compared with a control arm of standard triple antiretroviral drug treatment. Doubleblinded trials are preferable, but several antiretrovirals have been approved from open-label trials. Most regulatory clinical trials are designed to show the non-inferiority of the new antiretroviral versus standardof- care. The primary efficacy parameter is normally HIVRNAsuppression below 50 copies/mL by week 48, using a standardized efficacy endpoint (time to loss of virological response or confirmed virological response). If non-inferior efficacy is shown for the new antiretroviral, secondary analyses may then show other benefits, in terms of safety, convenience or drug resistance profiles. The antiretrovirals used in highly treatment-experienced patients are normally combined with a ‘background regimen’ of antiretrovirals, selected on the basis of drug resistance assays and treatment history. The results from trials in treatment-experienced patients are strongly dependent on baseline resistance profiles and the activity of the antiretrovirals used in the background regimen. The analysis of safety is well standardized, with toxicity grading systems for clinical and laboratory adverse events. Drug resistance at treatment failure could affect responses to second-line treatments. Where possible, patients should be followed-up after the failure of randomized medication, to assess longer term efficacy and safety outcomes on subsequent treatments.