How long after syphilis treatment do you retest for treatment response?

Syphilis Post-Treatment Retesting Schedule

For early syphilis (primary, secondary, or early latent), retest with nontreponemal tests (RPR/VDRL) at 6 and 12 months after treatment, with additional testing at 3,9, and 24 months recommended, particularly for HIV-infected patients. 1, 2, 3

Standard Follow-Up Intervals by Disease Stage

Early Syphilis (Primary, Secondary, Early Latent)

• Retest at 6 and 12 months after treatment as the minimum standard for all patients 2, 3
• More comprehensive monitoring at 3,6,9,12, and 24 months is recommended by the CDC, especially for HIV-infected patients 4, 1
• Treatment success is defined as a ≥4-fold decline in RPR titer within 6-12 months 1, 3, 5

Late Latent Syphilis

• Retest at 6,12,18, and 24 months after treatment 4, 1
• Expect a ≥4-fold decline in titer within 12-24 months (slower response than early syphilis) 1, 5, 6

Neurosyphilis

• CSF examination at 3 and 6 months after completion of therapy, then every 6 months until CSF white blood cell count normalizes and CSF-VDRL becomes nonreactive 4
• Monitor nontreponemal serum titers during the 12-24 months following treatment 4

HIV-Infected Patients: Critical Modifications

HIV-infected patients require more frequent monitoring at 3-month intervals rather than 6-month intervals due to higher rates of serologic treatment failure and increased risk for neurologic complications 1, 2, 3

• For early syphilis in HIV patients: test at 3,6,9,12, and 24 months 4, 1
• Consider CSF examination at 6 months post-therapy, particularly if CD4 count ≤350 cells/mL and/or RPR titer ≥1:32 1

Interpreting Treatment Response

Treatment Success

• ≥4-fold decline in nontreponemal titer is the key marker of adequate response 1, 3, 5
• For early syphilis: expect this decline within 6-12 months 1, 3, 6
• For late latent syphilis: expect this decline within 12-24 months 1, 5, 6

Serofast State (Not Treatment Failure)

• 15-20% of patients remain "serofast" with persistently low titers (usually <1:8) despite successful treatment 4, 1
• This does not represent treatment failure 4, 1
• Only ≥4-fold increase above the serofast baseline suggests reinfection 4, 1
• Complete seroreversion occurs in only 9.6% at 6 months and 17.1% at 12 months, even with appropriate treatment response 7

Treatment Failure Indicators

• No ≥4-fold decline in titer by 6-12 months (early syphilis) or 12-24 months (late latent) 4, 1
• Sustained ≥4-fold increase in titer after initial decline 4
• Persistent or recurring clinical signs/symptoms 4

Critical Testing Considerations

Laboratory Consistency

• Always use the same nontreponemal test method (RPR or VDRL) and preferably the same laboratory for serial monitoring 1, 2, 3
• Do not compare titers between different test types as they are not directly comparable 2, 3

When to Consider CSF Examination

• Nontreponemal titers fail to decrease by 6-9 months 1
• CD4 count ≤350 cells/mL and/or RPR titer ≥1:32 in HIV patients 1
• Any neurologic or ophthalmic symptoms develop 1
• Clinical signs or symptoms persist or recur 4, 3

Common Pitfalls to Avoid

• Do not assume persistent low-titer reactivity indicates treatment failure - the serofast state is common and expected 2, 3
• Do not use treponemal tests (FTA-ABS, TP-PA) to monitor treatment response - these remain positive for life regardless of cure 2
• Do not delay CSF examination in patients with inadequate serologic response - neurosyphilis can develop despite appropriate early syphilis treatment and initial serologic response 8
• Do not forget HIV testing - all patients with syphilis should be tested for HIV, as coinfection alters monitoring requirements 4, 2