As the authors point out, another important limitation relates to statistical power. Overall, a total of only 53 end points (deaths) occurred during the follow-up period. Even for the subgroup that formed the basis for their main conclusion, the 399 participants in the 0.201 to 0.350 × 109 cells/L subgroup, the distribution of the 33 end points, once adjusted for known confounding variables, did not achieve statistical significance (hazard ratio, 0.57; P = 0.16). To directly address the question of whether to defer therapy in patients with CD4+ T-cell counts greater than 0.200 × 109 cells/L would require a randomized trial of considerable size. For example, a study of treatment-naive patients with CD4+ T-cell counts greater than 0.250 × 109 cells/L, randomly assigned to immediate or deferred therapy, would require 650 events to show a 20% difference in mortality between groups with 80% power. At a rate of progression of 1% per year, 65 000 patient-years of follow-up or a study of 6500 patients for 10 years would be required. While studies of this size exist in other areas (11–12), they are the exception in HIV research.