One dose versus three weekly doses of benzathine penicillin G for patients co-infected with HIV and early syphilis: a multicenter, prospective observational study

PLoS One. 2014 Oct 6;9(10):e109667. doi: 10.1371/journal.pone.0109667. eCollection 2014.


Background: One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited.

Methods: We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3-6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%.

Results: Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4-72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3-79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17-3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38-2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20-2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively.

Conclusions: Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Coinfection*
  • Drug Administration Schedule
  • Female
  • HIV Infections / complications*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Penicillin G Benzathine / administration & dosage*
  • Penicillin G Benzathine / therapeutic use*
  • Prospective Studies
  • Syphilis / blood
  • Syphilis / complications*
  • Syphilis / drug therapy*


  • Penicillin G Benzathine

Grant support

This study was supported by grants from the Centers for Disease Control, Taiwan (grant number DOH102-DC-1401 to CCH). The funding source had no role in study design and conduct; data collection, analysis, or interpretation; or in the writing of the manuscript or the decision to submit it for publication.