Management of syphilis and HIV

Last updated: June 2013

Host immune responses are important in Syphilis as evidenced by the fact that in the pre-antibiotic era 60% of untreated individuals went through life without developing complications. Secondly while benzathine penicillin G and standard procaine penicillin G regimens do not achieve anti-treponemal levels in the CSF, neurosyphilis is uncommon in individuals treated with these regimens. Very careful neurological history and examination, including cranial nerve assessment, is required in all patients with syphilis.

Invasion of CSF by T. pallidum accompanied by CSF laboratory abnormalities is common among adults who have primary or secondary syphilis. Therefore, in immune-competent individuals in the absence of clinical neurologic findings, no evidence exists to support CSF examination or variation from the recommended treatment regimen for early syphilis.

The prognostic significance of asymptomatic laboratory defined neurosyphilis is unknown. CSF abnormalities (for example mononuclear pleocytosis and elevated protein levels) are common in HIV-infected persons, even in those without neurologic symptoms, although the clinical and prognostic significance of such CSF abnormalities with primary and secondary syphilis is unknown. Several studies have demonstrated that among persons infected with both HIV and syphilis, clinical and CSF abnormalities consistent with neurosyphilis are associated with a CD4 count of ≤350 cells/mL and/or an RPR titre of ≥1:32; however, unless neurologic symptoms are present, CSF examination in this setting has not been associated with improved clinical outcomes.

Recently expert opinion has questioned whether lumbar puncture adds to diagnosis or prognosis in asymptomatic HIV and syphilis co-infected individuals, with no signs of neurosyphilis. There is little evidence to support improvements in long term outcome from performing lumbar puncture and/or altering treatment regimens from those indicated for the same clinical stage of syphilis in HIV negative individuals but prudence would suggest that immune-compromised individuals be investigated for neurosyphilis.


CD4 >350 cells/mm3 and no neurological signs or symptoms

Treat as per stage of infection as for non HIV infected persons.

CD4 <350 cells/mm3and no neurological signs or symptoms

  • Lumbar puncture should be considered in the immune compromised and treatment should be guided by the results.
  • If lumbar puncture is not performed or is not accessible the treatment regimen will depend on the clinician’s assessment, taking into account:
    • presence or absence of neurological or other signs of tertiary syphilis
    • degree of immune-compromise
    • RPR titre
    • likely patient adherence to any regimen.

Any CD4 value and neurological signs or symptoms

  • Lumbar puncture is indicated
  • treatment is based on the findings of the lumbar puncture

Parameters indicating likely neurosyphilis

Reactive syphilis serology tests, symptoms or asymptomatic and ≥1 abnormal finding of the following on CSF:

  • WBC count >10 cells/microL
  • protein >50mg/dL
  • VDRL reactive.

Follow up

Definitive criteria for cure or failure have not been established but a 4 fold decrease in RPR in 6 to 12 months is a commonly used measure of success in early syphilis, and over longer periods in late latent syphilis.

A 4 fold increase in RPR is an indicator of either re-infection or treatment failure.

Non-treponemal test titres might decline more slowly for persons who have previously had syphilis.

Clinical and serologic evaluation should be performed at 1,3, 6, 12 and 24 months after treatment.

Consideration should be given to routine testing for syphilis at least annually in HIV infected persons with or without a past history of syphilis.

Further information

For further information on management of syphilis and HIV contact Adelaide Sexual Health Centre.


These guidelines are based on review of current literature, current recommendations of the United States Centers for Disease Control and Prevention, World Health Organization, the British Association for Sexual Health and HIV and local expert opinion.

They are written primarily for use by Adelaide Sexual Health Centre staff and some flexibility is required in applying them to certain private practice situations.