Interleukin‐2 in Clinical Trials: Other Factors to Be Considered

To the Editor—Emery et al. [1] did a valuable retrospective evaluation of 3 randomized controlled trials that addressed the clinical benefits of interleukin (IL)–2 therapy in adults with human immunodeficiency virus (HIV) infection. The analysis of the pooled data (median follow-up, 29 months) showed a nonsignificant but relevant 43% reduction in the risk of disease progression and death for subjects randomized to receive continuous infusion of IL-2, compared with those randomized to receive antiretroviral therapy alone (control group), even though 60% of the subjects in the control group received IL-2 after ∼1 year in the study. Another remarkable finding was the significantly lower plasma HIV RNA level for patients in the group receiving IL-2, relative to that for patients in the control group. A recent randomized multicenter clinical trial detected a larger decrease in the mean virus load and more likelihood of achieving a virus load of !50 copies/mL in subjects receiving IL-2, compared with subjects receiving antiretroviral therapy alone, at 1 year of follow-up [2]. Phase III trials of IL-2 therapy with antiretrovirals versus antiretroviral therapy alone are currently underway to appraise prospectively the role of IL-2 in HIV treatment. The results of these trials will be critical to defining the future use of IL-2 in this setting. Because the typical side effects of IL-2 therapy make a blinded study impossible, other aspects of the studies might affect the results. A meta-analysis [3] showed that several types of interventions (educational, behavioral, and emotional) had a weak-to-moderate effect on drug compliance and on outcomes for subjects with chronic diseases. In another study [4], patients with diabetes mellitus who believed that they had participated in the decision-making process were more likely to follow through on treatment decisions than those who did not feel that they were part of the decision-making process. An additional meta-analysis with diabetic patients found that emotional stability, internal and external motivations, perceived benefit, and supportive structure were positively associated with patient compliance [5]. Other factors that might be associated with better outcome include the amount of information and the encouragement that patients receive [6]. Subjects randomized to IL-2 therapy probably will have different experiences than subjects randomized to a control group (antiretroviral therapy alone). Those receiving IL-2 injections might make more-frequent visits to a doctor's office, as well as periodic phone calls to medical care providers, and therefore might have closer follow-up. This is reasonable to assume, …