What is the most appropriate management for a patient with a history of primary syphilis, currently on bictegravir (Integrase Strand Transfer Inhibitor)/emtricitabine (Nucleoside Reverse Transcriptase Inhibitor)/tenofovir alafenamide (Nucleotide Reverse Transcriptase Inhibitor), with stable Rapid Plasma Reagin (RPR) titers and no symptoms?

Management of Serofast Syphilis with Rising Titer in an HIV-Infected Patient

Obtain lumbar puncture and check cerebrospinal fluid-venereal disease research laboratory (Answer C)

This patient demonstrates a fourfold increase in RPR titer (from 1:4 to 1:8) after achieving initial serologic response, which indicates either treatment failure or reinfection and mandates CSF examination in HIV-infected patients according to CDC guidelines. 1

Clinical Reasoning

Understanding the Serologic Pattern

• This patient's RPR titers declined appropriately from 1:256 to 1:4 within 6 months of treatment, indicating initial treatment success 1
• The titers remained stable at 1:4 for one year (a "serofast" state), which is common and does not necessarily indicate treatment failure 2
• The critical finding is the doubling of titer from 1:4 to 1:8, representing a fourfold increase (two dilution change) above the established serofast baseline 1

Why CSF Examination is Required

• CDC guidelines explicitly state that when nontreponemal titers rise fourfold in HIV-infected patients, a repeat CSF examination should be performed and treatment administered accordingly 1
• A fourfold rise in titer above the established serofast baseline is considered indicative of potential reinfection or treatment failure, both requiring CSF evaluation in HIV-infected individuals 1, 3
• HIV-infected patients have an increased risk for neurosyphilis, and CSF abnormalities with poorer serologic responses have been documented in this population 1

Why Other Options Are Incorrect

• Option A (single dose benzathine penicillin): This would be appropriate for reinfection with early syphilis, but only after neurosyphilis has been excluded via CSF examination 3
• Option B (doxycycline): This is a penicillin-alternative for early syphilis in non-pregnant patients, but again requires excluding neurosyphilis first 4
• Option D (monitor without treatment): This is inappropriate given the fourfold titer increase, which demands evaluation and likely treatment 1

Clinical Approach Algorithm

1. Perform lumbar puncture immediately to obtain CSF-VDRL 1
2. If CSF is positive for neurosyphilis: Treat with aqueous crystalline penicillin G 18-24 million units daily for 10-14 days 1, 2
3. If CSF is negative: Treat with benzathine penicillin G 2.4 million units IM weekly for 3 weeks 1, 3
4. Follow-up: Monitor clinically and serologically at 3-month intervals (more frequent than the standard 6-month intervals for HIV-negative patients) 1, 2

Important Caveats

• The patient denies new sexual partners, but this does not eliminate the need for CSF examination—treatment failure and reinfection are managed similarly in HIV-infected patients with rising titers 1
• Even though the patient is asymptomatic, absence of neurologic symptoms does not exclude neurosyphilis in HIV-infected individuals 1
• The current ART regimen (bictegravir/emtricitabine/tenofovir alafenamide) is highly effective for HIV management but does not treat syphilis 5
• Sequential serologic tests should use the same testing method (RPR in this case) by the same laboratory to ensure accurate comparison 2