Syphilis treatment in the presence of HIV: the debate goes on

Curr Opin Infect Dis. 2015 Feb;28(1):44-52. doi: 10.1097/QCO.0000000000000132.


Purpose of review: Benzathine Penicillin G has been used to treat syphilis for over 50 years; however, the precise regimen of penicillin for treatment of syphilis in HIV-positive individuals remains a hot topic of debate. Although international guidelines recommend the same treatment for syphilis, regardless of HIV status, there are inconsistencies in prescribing practices among clinicians.

Recent findings: Two previous systematic reviews have found limited evidence for enhanced treatment of syphilis in the presence of HIV. However, a growing body of literature indicates that the rate of asymptomatic neurosyphilis may be higher in HIV, and that syphilis infection is associated with poorer long-term neurocognitive outcomes. A number of retrospective studies propose that serological response may be slower, or serological failure may be higher, among HIV-positive individuals, but these studies are limited by high loss to follow-up, high reinfection rates and a focus on serological rather than clinical response. Beyond penicillin, some evidence suggests equivalence of macrolides, cephalosporins and doxycycline, although macrolide resistance is an increasing concern.

Summary: Until a prospective, randomized study is conducted, inconsistency with treatment will continue. We offer a pragmatic approach to recognizing patients who may require further investigation or neuropenetrative antibiotic treatment.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Ceftriaxone / administration & dosage
  • Coinfection
  • Doxycycline / administration & dosage
  • Drug Resistance, Bacterial / drug effects*
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • Humans
  • Penicillin G Benzathine / administration & dosage*
  • Recurrence
  • Spinal Puncture / methods*
  • Syphilis / complications
  • Syphilis / drug therapy*
  • Syphilis / physiopathology
  • Syphilis Serodiagnosis
  • Treponema pallidum / drug effects*


  • Anti-Bacterial Agents
  • Ceftriaxone
  • Doxycycline
  • Penicillin G Benzathine