Syphilis management among HIV-infected persons: Difference between revisions
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{{Syphilis}} | {{Syphilis}} | ||
== Overview == | |||
Unusual serologic responses may be observed among HIV-infected persons who have syphilis. Both [[Syphilis laboratory findings#Treponemal test|treponemal]] and [[Syphilis laboratory findings#Nontreponemal test|nontreponemal serologic tests]] for syphilis should be interpreted in the usual manner for most patients who are coinfected with ''T. pallidum'' and [[HIV]]. HIV-positive patients should be treated with syphilis regimens recommended for HIV-negative patients. Careful follow-up after therapy is essential. HIV-positive patients who have early syphilis might be at increased risk for neurologic complications and may have higher rates of [[Syphilis laboratory findings#Serology|serologic]] treatment failure with currently recommended regimens. All HIV-infected persons with syphilis and [[Neurosyphilis#Clinical presentation: Four clinical types|neurologic symptoms]] should undergo immediate [[Syphilis laboratory findings#CSF analysis|CSF examination]]. | |||
==Management among HIV Infected Persons== | ==Management among HIV Infected Persons== | ||
===Diagnostic Considerations=== | ===Diagnostic Considerations=== | ||
*Although they are uncommon, unusual serologic responses have been observed among HIV-infected persons who have syphilis. Most reports have involved serologic titers that were higher than expected, but false-negative serologic test results and delayed appearance of seroreactivity also have been reported.<ref name="pmid15837859">Kingston AA, Vujevich J, Shapiro M, Hivnor CM, Jukic DM, Junkins-Hopkins JM et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15837859 Seronegative secondary syphilis in 2 patients coinfected with human immunodeficiency virus.] ''Arch Dermatol'' 141 (4):431-3. [http://dx.doi.org/10.1001/archderm.141.4.431 DOI:10.1001/archderm.141.4.431] PMID: [http://pubmed.gov/15837859 15837859]</ref> Regardless, both [[Syphilis laboratory findings#Treponemal test|treponemal]] and [[Syphilis laboratory findings#Nontreponemal test|nontreponemal serologic tests]] for syphilis can be interpreted in the usual manner for most patients who are coinfected with T. pallidum and [[HIV]].<ref name=cdc2015>http://www.cdc.gov/std/tg2015/references.htm#424 Accessed on September 27, 2016</ref> | *Although they are uncommon, unusual serologic responses have been observed among HIV-infected persons who have syphilis. Most reports have involved serologic titers that were higher than expected, but false-negative serologic test results and delayed appearance of seroreactivity also have been reported.<ref name="pmid15837859">Kingston AA, Vujevich J, Shapiro M, Hivnor CM, Jukic DM, Junkins-Hopkins JM et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15837859 Seronegative secondary syphilis in 2 patients coinfected with human immunodeficiency virus.] ''Arch Dermatol'' 141 (4):431-3. [http://dx.doi.org/10.1001/archderm.141.4.431 DOI:10.1001/archderm.141.4.431] PMID: [http://pubmed.gov/15837859 15837859]</ref> Regardless, both [[Syphilis laboratory findings#Treponemal test|treponemal]] and [[Syphilis laboratory findings#Nontreponemal test|nontreponemal serologic tests]] for syphilis can be interpreted in the usual manner for most patients who are coinfected with ''T. pallidum'' and [[HIV]].<ref name=cdc2015>http://www.cdc.gov/std/tg2015/references.htm#424 Accessed on September 27, 2016</ref> | ||
*When clinical findings are suggestive of syphilis but | *When clinical findings are suggestive of syphilis but serologic tests are nonreactive or their interpretation is unclear, alternative tests (e.g., biopsy of a lesion, [[Dark field microscopy|darkfield examination]], and [[Polymerase chain reaction|PCR]] of lesion material) might be useful for diagnosis. | ||
*[[Neurosyphilis]] should be considered in the differential diagnosis of neurologic disease in HIV-infected persons. | *[[Neurosyphilis]] should be considered in the differential diagnosis of neurologic disease in HIV-infected persons. | ||
===Treatment=== | ===Treatment=== | ||
*Compared with [[HIV]]-negative patients, HIV-positive patients who have early syphilis might be at increased risk for neurologic complications <ref name="urlSymptomatic Early Neurosyphilis Among HIV-Positive Men Who Have Sex with Men --- Four Cities, United States, January 2002--June 2004">{{cite web |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5625a1.htm |title=Symptomatic Early Neurosyphilis Among HIV-Positive Men Who Have Sex with Men --- Four Cities, United States, January 2002--June 2004 |format= |work= |accessdate=2012-12-19}}</ref> | *Compared with [[HIV]]-negative patients, HIV-positive patients who have early syphilis might be at increased risk for neurologic complications and may have higher rates of [[Syphilis laboratory findings#Serology|serologic]] treatment failure with currently recommended regimens.<ref name="urlSymptomatic Early Neurosyphilis Among HIV-Positive Men Who Have Sex with Men --- Four Cities, United States, January 2002--June 2004">{{cite web |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5625a1.htm |title=Symptomatic Early Neurosyphilis Among HIV-Positive Men Who Have Sex with Men --- Four Cities, United States, January 2002--June 2004 |format= |work= |accessdate=2012-12-19}}</ref> The magnitude of these risks is not defined precisely, but is likely small.<ref name=cdc2015>http://www.cdc.gov/std/tg2015/references.htm#424 Accessed on September 27, 2016</ref> | ||
*No treatment regimens for syphilis have been demonstrated to be more effective in preventing [[neurosyphilis]] in HIV-infected patients than the syphilis regimens recommended for HIV-negative patients.<ref name="pmid9235493">Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M et al. (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9235493 A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group.] ''N Engl J Med'' 337 (5):307-14. [http://dx.doi.org/10.1056/NEJM199707313370504 DOI:10.1056/NEJM199707313370504] PMID: [http://pubmed.gov/9235493 9235493]</ref> | *No treatment regimens for syphilis have been demonstrated to be more effective in preventing [[neurosyphilis]] in HIV-infected patients than the syphilis regimens recommended for HIV-negative patients.<ref name="pmid9235493">Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M et al. (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9235493 A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group.] ''N Engl J Med'' 337 (5):307-14. [http://dx.doi.org/10.1056/NEJM199707313370504 DOI:10.1056/NEJM199707313370504] PMID: [http://pubmed.gov/9235493 9235493]</ref> | ||
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*Several studies have demonstrated that among persons infected with both HIV and syphilis, [[Syphilis physical examination|clinical]] and [[Syphilis laboratory findings#CSF analysis|CSF abnormalities]] consistent with [[neurosyphilis]] are associated with a [[CD4|CD4 count]] of ≤350 cells/mL and/or an [[rapid plasma reagent|RPR titer]] of ≥1:32;<ref name="pmid14745693">Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14745693 Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features.] ''J Infect Dis'' 189 (3):369-76. [http://dx.doi.org/10.1086/381227 DOI:10.1086/381227] PMID: [http://pubmed.gov/14745693 14745693]</ref><ref name="pmid16865051">Libois A, De Wit S, Poll B, Garcia F, Florence E, Del Rio A et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16865051 HIV and syphilis: when to perform a lumbar puncture.] ''Sex Transm Dis'' 34 (3):141-4. [http://dx.doi.org/10.1097/01.olq.0000230481.28936.e5 DOI:10.1097/01.olq.0000230481.28936.e5] PMID: [http://pubmed.gov/16865051 16865051]</ref><ref name="pmid19187028">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2009) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19187028 Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms.] ''Clin Infect Dis'' 48 (6):816-21. [http://dx.doi.org/10.1086/597096 DOI:10.1086/597096] PMID: [http://pubmed.gov/19187028 19187028]</ref> however, unless neurologic symptoms are present, [[Syphilis laboratory findings#CSF analysis|CSF examination]] in this setting has not been associated with improved clinical outcomes. | *Several studies have demonstrated that among persons infected with both HIV and syphilis, [[Syphilis physical examination|clinical]] and [[Syphilis laboratory findings#CSF analysis|CSF abnormalities]] consistent with [[neurosyphilis]] are associated with a [[CD4|CD4 count]] of ≤350 cells/mL and/or an [[rapid plasma reagent|RPR titer]] of ≥1:32;<ref name="pmid14745693">Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14745693 Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features.] ''J Infect Dis'' 189 (3):369-76. [http://dx.doi.org/10.1086/381227 DOI:10.1086/381227] PMID: [http://pubmed.gov/14745693 14745693]</ref><ref name="pmid16865051">Libois A, De Wit S, Poll B, Garcia F, Florence E, Del Rio A et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16865051 HIV and syphilis: when to perform a lumbar puncture.] ''Sex Transm Dis'' 34 (3):141-4. [http://dx.doi.org/10.1097/01.olq.0000230481.28936.e5 DOI:10.1097/01.olq.0000230481.28936.e5] PMID: [http://pubmed.gov/16865051 16865051]</ref><ref name="pmid19187028">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2009) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19187028 Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms.] ''Clin Infect Dis'' 48 (6):816-21. [http://dx.doi.org/10.1086/597096 DOI:10.1086/597096] PMID: [http://pubmed.gov/19187028 19187028]</ref> however, unless neurologic symptoms are present, [[Syphilis laboratory findings#CSF analysis|CSF examination]] in this setting has not been associated with improved clinical outcomes. | ||
*The use of [[AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral therapy]] as per current guidelines | *The use of [[AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral therapy]] as per current guidelines may improve clinical outcomes in [[HIV]]-infected persons with syphilis.<ref name="pmid18715154">Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18715154 Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis.] ''Clin Infect Dis'' 47 (7):893-9. [http://dx.doi.org/10.1086/591534 DOI:10.1086/591534] PMID: [http://pubmed.gov/18715154 18715154]</ref><ref name="pmid18525260">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18525260 Neurosyphilis in a clinical cohort of HIV-1-infected patients.] ''AIDS'' 22 (10):1145-51. [http://dx.doi.org/10.1097/QAD.0b013e32830184df DOI:10.1097/QAD.0b013e32830184df] PMID: [http://pubmed.gov/18525260 18525260]</ref><ref name="pmid18532887">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18532887 Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients.] ''Clin Infect Dis'' 47 (2):258-65. [http://dx.doi.org/10.1086/589295 DOI:10.1086/589295] PMID: [http://pubmed.gov/18532887 18532887]</ref> | ||
====Special Considerations==== | ====Special Considerations==== | ||
Revision as of 19:19, 14 October 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]; Nate Michalak, B.A.
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Overview
Unusual serologic responses may be observed among HIV-infected persons who have syphilis. Both treponemal and nontreponemal serologic tests for syphilis should be interpreted in the usual manner for most patients who are coinfected with T. pallidum and HIV. HIV-positive patients should be treated with syphilis regimens recommended for HIV-negative patients. Careful follow-up after therapy is essential. HIV-positive patients who have early syphilis might be at increased risk for neurologic complications and may have higher rates of serologic treatment failure with currently recommended regimens. All HIV-infected persons with syphilis and neurologic symptoms should undergo immediate CSF examination.
Management among HIV Infected Persons
Diagnostic Considerations
- Although they are uncommon, unusual serologic responses have been observed among HIV-infected persons who have syphilis. Most reports have involved serologic titers that were higher than expected, but false-negative serologic test results and delayed appearance of seroreactivity also have been reported.[1] Regardless, both treponemal and nontreponemal serologic tests for syphilis can be interpreted in the usual manner for most patients who are coinfected with T. pallidum and HIV.[2]
- When clinical findings are suggestive of syphilis but serologic tests are nonreactive or their interpretation is unclear, alternative tests (e.g., biopsy of a lesion, darkfield examination, and PCR of lesion material) might be useful for diagnosis.
- Neurosyphilis should be considered in the differential diagnosis of neurologic disease in HIV-infected persons.
Treatment
- Compared with HIV-negative patients, HIV-positive patients who have early syphilis might be at increased risk for neurologic complications and may have higher rates of serologic treatment failure with currently recommended regimens.[3] The magnitude of these risks is not defined precisely, but is likely small.[2]
- No treatment regimens for syphilis have been demonstrated to be more effective in preventing neurosyphilis in HIV-infected patients than the syphilis regimens recommended for HIV-negative patients.[4]
- Careful follow-up after therapy is essential.
Primary and Secondary Syphilis Among HIV-Infected Persons
Recommended regimen
- Benzathine penicillin G, 2.4 million units IM in a single dose.
- Available data demonstrate that additional doses of benzathine penicillin G, amoxicillin, or other antibiotics in early syphilis do not result in enhanced efficacy, regardless of HIV status.[4]
Other Management Considerations
- Most HIV-infected persons respond appropriately to standard benzathine penicillin for primary and secondary syphilis.
- CSF abnormalities (e.g., 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 titer of ≥1:32;[5][6][7] however, unless neurologic symptoms are present, CSF examination in this setting has not been associated with improved clinical outcomes.
- The use of antiretroviral therapy as per current guidelines may improve clinical outcomes in HIV-infected persons with syphilis.[8][9][10]
Special Considerations
- HIV-infected, penicillin-allergic patients who have primary or secondary syphilis should be managed according to the recommendations for penicillin-allergic, HIV-negative patients.
- Patients with penicillin allergy whose compliance with therapy or follow-up cannot be ensured should be desensitized and treated with penicillin.
- The use of alternatives to penicillin has not been well studied in HIV-infected patients. These therapies should be used only in conjunction with close serologic and clinical follow-up.
Follow-Up
- HIV-infected persons should be evaluated clinical and serologically for treatment failure at 3, 6, 9, 12, and 24 months after therapy.
- HIV-infected persons who meet the criteria for treatment failure (i.e., signs or symptoms that persist or recur or persons who have a sustained fourfold increase in nontreponemal test titer) should be managed in the same manner as HIV-negative patients (i.e., a CSF examination and retreatment).
- CSF examination and re-treatment also should be strongly considered for persons whose nontreponemal test titer do not decrease fourfold within 6-12 months of therapy.
- If CSF examination is normal, treatment with benzathine penicillin G administered as 2.4 million units IM each at weekly intervals for 3 weeks is recommended.
Latent Syphilis Among HIV-Infected Persons
Treatment
- HIV-infected persons with latent syphilis should be treated according to the stage-specific recommendations for HIV-negative persons.
- Treatment of early latent syphilis among HIV-infected persons is benzathine penicillin G, 2.4 million units IM in a single dose.
- Treatment of late latent syphilis or syphilis of unknown duration among HIV-infected persons is benzathine penicillin G, at weekly doses of 2.4 million units for 3 weeks.
Other Management Considerations
- All HIV-infected persons with syphilis and neurologic symptoms should undergo immediate CSF examination.
- Some studies have demonstrated that clinical and CSF abnormalities consistent with neurosyphilis are most likely in HIV-infected persons who have been diagnosed with syphilis and have a CD4 count of ≤350 cells/ml and/or an RPR titer of ≥1:32;[5][6][7] however unless neurologic symptoms are present, CSF examination in this setting has not been associated with improved clinical outcomes.
Special Considerations
- The efficacy of alternative non-penicillin regimens in HIV-infected persons has not been well studied.[2]
- Patients with penicillin allergy whose compliance with therapy or follow-up cannot be ensured should be desensitized and treated with penicillin.
- Limited clinical studies, along with biologic and pharmacologic evidence, suggest that ceftriaxone might be effective.[11][12] However, the optimal dose and duration of ceftriaxone therapy have not been defined.
Follow-Up
- Patients should be evaluated clinically and serologically at 6, 12, 18, and 24 months after therapy.
- If, at any time, clinical symptoms develop or nontreponemal titers rise fourfold, a repeat CSF examination should be performed and treatment administered accordingly.
- If during 12-24 months the nontreponemal titer does not decline fourfold, CSF examination should be strongly considered and treatment administered accordingly.
Neurosyphilis Among HIV-Infected Persons
Treatment
HIV-infected patients with neurosyphilis should be treated according to the recommendations for HIV-negative patients with neurosyphilis.
Special Considerations
- HIV-infected, penicillin-allergic patients who have neurosyphilis should be managed according to the recommendations for penicillin-allergic, HIV-negative patients with neurosyphilis.
- Several small observational studies conducted in HIV-infected patients with neurosyphilis suggest that ceftriaxone 1-2 g IV daily for 10-14 days might be effective as an alternate agent.[11][12][10]
Follow-up
- If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal.
- Follow-up CSF examinations also can be used to gauge response after therapy.
- Limited data suggest that changes in CSF parameters might occur more slowly in HIV-infected patients, especially those with more advanced immunosuppression.[13][9]
- If the cell count has not decreased after 6 months or if the CSF is not normal after 2 years, retreatment should be considered.
References
- ↑ Kingston AA, Vujevich J, Shapiro M, Hivnor CM, Jukic DM, Junkins-Hopkins JM et al. (2005) Seronegative secondary syphilis in 2 patients coinfected with human immunodeficiency virus. Arch Dermatol 141 (4):431-3. DOI:10.1001/archderm.141.4.431 PMID: 15837859
- ↑ 2.0 2.1 2.2 http://www.cdc.gov/std/tg2015/references.htm#424 Accessed on September 27, 2016
- ↑ "Symptomatic Early Neurosyphilis Among HIV-Positive Men Who Have Sex with Men --- Four Cities, United States, January 2002--June 2004". Retrieved 2012-12-19.
- ↑ 4.0 4.1 Rolfs RT, Joesoef MR, Hendershot EF, Rompalo AM, Augenbraun MH, Chiu M et al. (1997) A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. N Engl J Med 337 (5):307-14. DOI:10.1056/NEJM199707313370504 PMID: 9235493
- ↑ 5.0 5.1 Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M et al. (2004) Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 189 (3):369-76. DOI:10.1086/381227 PMID: 14745693
- ↑ 6.0 6.1 Libois A, De Wit S, Poll B, Garcia F, Florence E, Del Rio A et al. (2007) HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis 34 (3):141-4. DOI:10.1097/01.olq.0000230481.28936.e5 PMID: 16865051
- ↑ 7.0 7.1 Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2009) Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms. Clin Infect Dis 48 (6):816-21. DOI:10.1086/597096 PMID: 19187028
- ↑ Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA (2008) Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. Clin Infect Dis 47 (7):893-9. DOI:10.1086/591534 PMID: 18715154
- ↑ 9.0 9.1 Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS 22 (10):1145-51. DOI:10.1097/QAD.0b013e32830184df PMID: 18525260
- ↑ 10.0 10.1 Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients. Clin Infect Dis 47 (2):258-65. DOI:10.1086/589295 PMID: 18532887
- ↑ 11.0 11.1 Dowell ME, Ross PG, Musher DM, Cate TR, Baughn RE (1992) Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. Am J Med 93 (5):481-8. PMID: 1442850
- ↑ 12.0 12.1 Smith NH, Musher DM, Huang DB, Rodriguez PS, Dowell ME, Ace W et al. (2004) Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin. Int J STD AIDS 15 (5):328-32. DOI:10.1258/095646204323012823 PMID: 15117503
- ↑ Marra CM, Maxwell CL, Tantalo L, Eaton M, Rompalo AM, Raines C et al. (2004) Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter? Clin Infect Dis 38 (7):1001-6. DOI:10.1086/382532 PMID: 15034833