Effectiveness of Syphilis Treatment Using Azithromycin and/or Benzathine Penicillin in Rakai, Uganda

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Abstract
The goal of this study was to assess azithromycin and/or benzathine penicillin for treatment of syphilis. In a population-based study, participants with serologic syphilis (TRUST with TPHA confirmation) were offered 2.4 MU benzathine penicillin intramuscularly. Intervention arm participants received 1 g presumptive oral azithromycin. We assessed cure rates with penicillin or azithromycin given alone and in combination. Cure assessed after 10 months was defined as seroreversion or a 4-fold decrease in titer. The rate ratio (RR) of cure and 95% confidence intervals (95% CIs) were estimated by log binomial regression. Among 952 cases with syphilis, 18% received penicillin alone, 17% azithromycin only, and 65% dual treatment. The overall cure rate was 61%. Cure rates were lower in males compared with females (RR, 0.89; 95% CI, 0.80–0.99) and in subjects with initial titers ≥1:4 compared with ≤1:2 (RR, 0.77; 95% CI, 0.69–0.86). There was no significant differences in cure rates among HIV-positive and HIV-negative persons. With initial titers ≤1:2, there were no differences in cure rates by treatment regimen. However, with initial titers ≥1:4, significantly higher cure rates were observed with azithromycin alone (adjusted RR, 1.38; 95% CI, 0.97–1.96), and with dual treatment of azithromycin and benzathine penicillin (RR, 1.38; 95% CI, 1.03–1.87) compared with penicillin alone. Azithromycin alone or in combination with penicillin achieved higher cure rates than penicillin alone in cases with a high initial TRUST titer. In low-titer infections, the 3 drug combinations were equally effective. HIV status did not affect cure rates.