Objective Serologic tests for syphilis (STS) results at the time of diagnosis are the basis for evaluating response to syphilis therapy. Following treatment, however, STS titres may continue to increase for several weeks. In a recent study comparing azithromycin to penicillin or doxycycline for early syphilis treatment, patients had RPR titres measured initially, at 7 and at 14 days following treatment. We evaluated variation in RPR titres over the 14 days following therapy, hypothesising that RPR titre changes would vary with stage and initial titre.

Methods Prospectively identified HIV-seronegative participants at five North American and three Madagascar sites with primary, secondary or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy) or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 post-treatment. All RPR titres were determined simultaneously at a central laboratory. Analysis was done using SAS 9.2.

Results 465 patients had data available for at least 2 of 3 RPR measurements. Median RPR at diagnosis by stage was Primary 1:16, Secondary 1:64, Early Latent 1:32. Overall, 20% of patients showed a titre increase of at least one dilution in the 14 days following therapy. Of this group, 88.2% demonstrated an increase of 1 dilution, while 11.8% demonstrated an increase of ≥2 dilutions. The greatest proportion of titre increases following therapy was seen in patients with primary syphilis.

Conclusions Given the reliance upon changes in RPR titres for evaluating response to therapy, these changes in titre following therapy could affect whether a response is classified as treatment success/failure or serofast status. Further analyses will evaluate factors associated with increasing RPR titres following therapy, as well as the effect of these changes in titre on evaluation of response to therapy.