Syphilis Among Persons with HIV Infection

Diagnostic Considerations

Interpretation of treponemal and nontreponemal serologic tests for persons with HIV infection is the same as for persons without HIV. Although rare, unusual serologic responses have been observed among persons with HIV infection who have syphilis. The majority of reports have involved posttreatment serologic titers that were higher than expected (i.e., high serofast) or fluctuated, and false-negative serologic test results and delayed appearance of seroreactivity have also been reported (622).

When clinical findings are indicative of syphilis, but serologic tests are nonreactive or their interpretation is unclear, alternative tests (e.g., biopsy of a lesion, darkfield examination, or PCR of lesion material) might be useful for diagnosis. Neurosyphilis, ocular syphilis, and otosyphilis should be considered in the differential diagnosis of neurologic, ocular, and other signs and symptoms among persons with HIV infection.

Treatment

Persons with HIV infection who have early syphilis might be at increased risk for neurologic complications (623) and might have higher rates of inadequate serologic response with recommended regimens. The magnitude of these risks is not defined precisely but is likely small. Although long-term (>1 year) comparative data are lacking, no treatment regimens for syphilis have been demonstrated to be more effective in preventing neurosyphilis among persons with HIV infection than the syphilis regimens recommended for persons without HIV (609). Careful follow-up after therapy is essential. Using ART per current HIV guidelines might improve clinical outcomes among persons coinfected with HIV and syphilis; concerns regarding adequate treatment of syphilis among persons with HIV infection might not apply to those with HIV virologic suppression (624,625).

Primary and Secondary Syphilis Among Persons with HIV Infection

Available data demonstrate that additional doses of benzathine penicillin G, amoxicillin, or other antibiotics in primary and secondary syphilis among persons with HIV infection do not result in enhanced efficacy (592,593,609).

Other Management Considerations

The majority of persons with HIV infection respond appropriately to the recommended benzathine penicillin G treatment regimen for primary and secondary syphilis (626). CSF abnormalities (e.g., mononuclear pleocytosis and elevated protein levels) can be common among persons with HIV, even those without syphilis. The clinical and prognostic significance of such CSF laboratory abnormalities among persons with primary and secondary syphilis who lack neurologic symptoms is unknown. Certain studies have demonstrated that among persons with HIV infection and syphilis, CSF abnormalities are associated with a CD4⁺ T-cell count of ≤350 cells/mL or an RPR titer of ≥1:32 (614,627). However, CSF examination followed by treatment for neurosyphilis on the basis of laboratory abnormalities has not been associated with improved clinical outcomes in the absence of neurologic signs and symptoms. All persons with HIV infection and primary and secondary syphilis should have a thorough neurologic, ocular, and otic examination (614,622,625). CSF examination should be reserved for those with an abnormal neurologic examination.

Follow-Up

Persons with HIV infection and primary or secondary syphilis should be evaluated clinically and serologically for possible treatment failure at 3, 6, 9, 12, and 24 months after therapy; those who meet the criteria for treatment failure (i.e., signs or symptoms that persist or recur or a sustained [>2 weeks] fourfold or greater increase in titer) should be managed in the same manner as persons without HIV infection (i.e., depending on history of sexual activity and on findings of neurologic examination, either repeat treatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks or CSF examination and repeat treatment guided by CSF findings) (see Primary and Secondary Syphilis).

In addition, CSF examination and retreatment can be considered for persons whose nontreponemal test titers do not decrease fourfold within 24 months of therapy. If CSF examination is normal, treatment with benzathine penicillin G administered as 2.4 million units IM at weekly intervals for 3 weeks is recommended. Serologic titers might not decrease despite a negative CSF examination and a repeated 3-week course of therapy (599). Especially if the initial nontreponemal titer is low (<1:8) in these circumstances, the benefit of additional therapy or repeated CSF examinations is unclear but is not usually recommended. Serologic and clinical monitoring at least annually should continue to monitor for any sustained increases in nontreponemal titer.

Management of Sex Partners

See Syphilis, Management of Sex Partners.

Special Considerations

Penicillin Allergy

Persons with HIV infection who are allergic to penicillin and have primary or secondary syphilis should be managed according to the recommendations for persons without HIV who are allergic to penicillin (see Primary and Secondary Syphilis). Persons with penicillin allergy whose compliance with alternative therapy or follow-up cannot be ensured should be desensitized and treated with penicillin G (see Management of Persons Who Have a History of Penicillin Allergy). Using penicillin alternatives has not been well studied among persons with HIV infection; azithromycin is not recommended for persons with HIV and primary or secondary syphilis infection. Alternative therapies should be used only in conjunction with close serologic and clinical follow-up. Persons with HIV and latent syphilis should be treated similarly to persons who do not have HIV (see Latent Syphilis).

Latent Syphilis Among Persons with HIV Infection

Other Management Considerations

All persons with HIV and latent syphilis infection should undergo a thorough neurologic, ocular, and otic examination; those with neurologic symptoms or signs should undergo immediate CSF examination. In the absence of neurologic symptoms or signs, CSF examination has not been associated with improved clinical outcomes and therefore is not recommended. Those with ocular or otic symptoms or signs should be evaluated for ocular syphilis and otosyphilis according to those clinical presentations (see Neurosyphilis, Ocular Syphilis, and Otosyphilis).

Follow-Up

Patients with HIV and latent syphilis infection should be evaluated clinically and serologically at 6, 12, 18, and 24 months after therapy. Those persons who meet the criteria for treatment failure (i.e., signs or symptoms that persist or recur or a sustained [>2 weeks] fourfold or greater increase in titer) should be managed in the same manner as persons without HIV (i.e., depending on history of sexual activity and on findings of neurologic examination, either repeat treatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks or CSF examination and repeat treatment guided by CSF findings) (see Latent Syphilis).

In addition, CSF examination and retreatment can be considered for persons whose nontreponemal test titers do not decrease fourfold within 24 months of therapy. If CSF examination is normal, treatment with benzathine penicillin G administered as 2.4 million units IM at weekly intervals for 3 weeks is recommended. Serologic titers might not decrease despite a negative CSF examination and a repeated 3-week course of therapy (599). Especially if the initial nontreponemal titer is low (<1:8) in these circumstances, the benefit of additional therapy or repeated CSF examinations is unclear but is not usually recommended. Serologic and clinical monitoring at least annually should continue to ensure nontreponemal titers remain stable without any sustained titer increases.

Management of Sex Partners

See Syphilis, Management of Sex Partners.

Special Considerations

Penicillin Allergy

The efficacy of alternative nonpenicillin regimens for latent syphilis for persons living with HIV infection has not been well studied, and these therapies should be used only in conjunction with close serologic and clinical follow-up. Patients with penicillin allergy whose compliance with alternative therapy or follow-up cannot be ensured should be desensitized and treated with penicillin G (see Management of Persons Who Have a History of Penicillin Allergy).

Neurosyphilis, Ocular Syphilis, and Otic Syphilis Among Persons with HIV Infection

All persons with HIV and syphilis coinfection should receive a careful neurologic ocular and otic examination. Persons with HIV infection and neurosyphilis should be treated according to the recommendations for persons with neurosyphilis and without HIV infection (see Neurosyphilis, Ocular Syphilis, and Otosyphilis).

Follow-Up

Persons with HIV and neurosyphilis infection should be managed according to the recommendations for persons without HIV infection. Serum RPR can be followed for necessary treatment success rather than following CSF parameters (see Neurosyphilis, Ocular Syphilis, and Otosyphilis). Limited data indicate that changes in CSF parameters might occur more slowly among persons with HIV infection, especially those with more advanced immunosuppression (588,624).

Management of Sex Partners

See Syphilis, Management of Sex Partners.

Special Considerations

Penicillin Allergy

Persons with HIV who are allergic to penicillin and have neurosyphilis infection should be managed according to the recommendations for persons without HIV infection with neurosyphilis who are allergic to penicillin (see Neurosyphilis, Ocular Syphilis, and Otosyphilis). Small observational studies conducted among persons with HIV and neurosyphilis report that ceftriaxone 1–2 g IV daily for 10–14 days might be effective as an alternative agent (628–630). The possibility of cross-sensitivity between ceftriaxone and penicillin exists; however, the risk for penicillin cross-reactivity between third-generation cephalosporins is negligible (619–621,631) (see Management of Persons Who Have a History of Penicillin Allergy). If concern exists regarding the safety of ceftriaxone for a person with HIV and neurosyphilis, skin testing should be performed to confirm penicillin allergy and, if necessary, penicillin desensitization in consultation with a specialist is recommended. Other regimens have not been adequately evaluated for treatment of neurosyphilis.

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