Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial

Clin Infect Dis. 2017 Mar 15;64(6):759-764. doi: 10.1093/cid/ciw862.


Background: Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients.

Methods: We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period.

Results: Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results.

Conclusions: When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis.

Clinical trials registration: NCT02611765.

Keywords: HIV; benzathine penicillin; clinical trial.; syphilis.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Female
  • HIV Infections / complications*
  • Humans
  • Injections, Intramuscular
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Penicillin G Benzathine / administration & dosage*
  • Prospective Studies
  • Reagins / blood
  • Syphilis / drug therapy*
  • Treatment Outcome
  • Young Adult


  • Anti-Bacterial Agents
  • Reagins
  • Penicillin G Benzathine

Associated data