Treatment of Early Syphilis

To the Editor—Andrade and colleagues addressed an important clinical issue in their randomized study of 1 vs 3 penicillin injections for human immunodeficiency virus (HIV)–infected patients with early syphilis [1]. However, there remain several questions. First, the estimated difference in treatment success between the 2 arms was substantial (95% vs 75%), resulting in the calculation of a moderate sample size of 108 patients for the study. However, the literature does not give any evidence that 20% of differences in the outcome have to be expected between the enhanced vs standard group [2]. Nevertheless, the authors were not able to fully enroll the study and finally closed on only 64 patients. The allocation of patients to the 2 study arms was not sufficiently balanced. Fifty-five percent were treated with 1 penicillin injection and 45% with 3 penicillin injections. Furthermore, the geometric means of the rapid plasma reagin (RPR) titers at baseline were not well balanced (116 vs 78, respectively). Both the sample size calculations and the imbalances in study patients severely impact the clinical significance of the study. Moreover, the response rates after 12 months differed substantially between groups (80% vs 93%). As the conception for the trial was not a noninferiority study, the results do not allow the conclusion that 1 injection of penicillin is not inferior to 3 injections. Taken together, we cannot agree with the authors' conclusion that a larger study would only detect a small but clinically insignificant difference in treatment outcome.