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Does directly observed therapy improve outcomes in treatment-naive patients? Is a once-daily regimen more effective than a twice-daily one? In ACTG 5073, 402 treatment-naive patients were randomized to receive a lopinavir/ritonavir-based regimen in one of three ways: self-administered, once daily; self-administered, twice daily; or directly observed, once daily [Abstract 138]. Overall, no differences were seen between study arms in time to virologic failure. An unanticipated finding was that the once-daily self-administered regimen had reduced efficacy (compared with the twice-daily regimen) in patients with baseline viral loads >100,000 copies/mL, a result not seen in prior studies of once-daily lopinavir/r. As with many studies that were …