Gross et al1 reported no benefit from directly administered antiretroviral therapy (DAART) among antiretroviral-naive patients enrolled in a randomized controlled trial (RCT). They should be commended for using the rigors of an RCT, yet serious concerns remain in their choice of study population and use of an untested DAART intervention.
The use of a single regimen, testing the durability of DAART, monitoring adherence using Medication Event Monitoring System (MEMS) caps (Aardex Corp, Zug, Switzerland), and examining genotypic resistance are major strengths of this trial. Highly motivated, antiretroviral-naive subjects enrolled in clinical trials are probably the least likely population, however, to benefit from an adherence intervention. Correlates of problematic adherence (eg, active drug use, untreated mental illness, prior antiretroviral experience, and cognitive impairment) were known long before subject accrual.2 Why, then, were they studied? After considerable costs to patients and taxpayers, we learned what we already knew from previous RCTs—DAART is not effective among subjects without predictors of nonadherence,3 while others benefit greatly.4,5 Arguably, DAART patients were not harmed. All of them, however, were potentially inconvenienced, and one-third reported the intervention not to be helpful. With increasing recognition of costs, it is highly unlikely that costly DAART interventions would ever be considered for this group. Moreover, this study was undertaken in an idealized fashion, with a highly selected group of patients, with little attention given to ensure that the results are applicable in real-world settings.