Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Epidemiology, clinical presentation, and diagnosis of syphilis in the HIV-infected patient

Anne Rompalo, MD
Section Editor
Noreen A Hynes, MD, MPH, DTM&H
Deputy Editor
Jennifer Mitty, MD, MPH


Syphilis is a sexually acquired infection, which is characterized by episodes of active clinical disease interrupted by periods of latent infection, if left untreated. Studies suggest that HIV infection modulates the clinical presentation of syphilis with greater organ involvement, atypical and florid skin rashes, and more rapid progression to neurosyphilis. The results of serologic tests for syphilis may also be modified in HIV-infected patients. Furthermore, emerging data suggest that syphilis may have a negative impact on HIV viral load.

The clinical presentation of syphilis in the HIV-infected patient will be reviewed here. The diagnosis and treatment of the HIV-infected patient with syphilis and syphilis in immunocompetent patients and other hosts are discussed separately. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients" and "Syphilis: Treatment and monitoring" and "Syphilis: Screening and diagnostic testing" and "Treatment and prevention of syphilis in the HIV-infected patient".)


Syphilis is caused by the spirochete Treponema pallidum subspecies pallidum, a corkscrew-shaped, microaerophilic bacterium, which cannot be cultivated in the laboratory. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Microbiology'.)

Because of the inability to grow T. pallidum in culture, the diagnosis of syphilis depends upon the sexual exposure history, recognition of protean clinical signs and symptoms, and interpretation of diagnostic testing.


Although the rates of primary and secondary syphilis in the United States declined 90 percent from 1990 to 2000, the rates increased annually from 2001 to 2009. In 2013, the rate of reported primary and secondary syphilis in the United States was 5.3 cases per 100,000 population [1], more than double the lowest-ever rate of 2.1 in 2000 [2]. The largest increase in the number of syphilis cases has occurred among men who have sex with men (MSM). The increasing incidence of syphilis in this population is due in part to rising rates of risky sexual behaviors, such as anonymous sex, unprotected sex (oral and anal), sex with multiple partners, and/or sex under the influence of drugs, especially methamphetamine [3-9].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: May 2017. | This topic last updated: Apr 23, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Patton ME, Su JR, Nelson R, et al. Primary and secondary syphilis--United States, 2005-2013. MMWR Morb Mortal Wkly Rep 2014; 63:402.
  2. Centers for Disease Control and Prevention. 2009 Sexually Transmitted Diseases Surveillance. http://www.cdc.gov/std/stats09/default.htm (Accessed on August 03, 2011).
  3. Taylor MM, Aynalem G, Smith LV, et al. Methamphetamine use and sexual risk behaviours among men who have sex with men diagnosed with early syphilis in Los Angeles County. Int J STD AIDS 2007; 18:93.
  4. Centers for Disease Control and Prevention (CDC). Methamphetamine use and HIV risk behaviors among heterosexual men--preliminary results from five northern California counties, December 2001-November 2003. MMWR Morb Mortal Wkly Rep 2006; 55:273.
  5. Spindler HH, Scheer S, Chen SY, et al. Viagra, methamphetamine, and HIV risk: results from a probability sample of MSM, San Francisco. Sex Transm Dis 2007; 34:586.
  6. Wong W, Chaw JK, Kent CK, Klausner JD. Risk factors for early syphilis among gay and bisexual men seen in an STD clinic: San Francisco, 2002-2003. Sex Transm Dis 2005; 32:458.
  7. Centers for Disease Control and Prevention (CDC). Transmission of primary and secondary syphilis by oral sex--Chicago, Illinois, 1998-2002. MMWR Morb Mortal Wkly Rep 2004; 53:966.
  8. Thurnheer MC, Weber R, Toutous-Trellu L, et al. Occurrence, risk factors, diagnosis and treatment of syphilis in the prospective observational Swiss HIV Cohort Study. AIDS 2010; 24:1907.
  9. Page-Shafer K, Shiboski CH, Osmond DH, et al. Risk of HIV infection attributable to oral sex among men who have sex with men and in the population of men who have sex with men. AIDS 2002; 16:2350.
  10. Ganesan A, Fieberg A, Agan BK, et al. Results of a 25-year longitudinal analysis of the serologic incidence of syphilis in a cohort of HIV-infected patients with unrestricted access to care. Sex Transm Dis 2012; 39:440.
  11. Wasserheit JN. Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis 1992; 19:61.
  12. Røttingen JA, Cameron DW, Garnett GP. A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much really is known? Sex Transm Dis 2001; 28:579.
  13. Buchacz K, Klausner JD, Kerndt PR, et al. HIV incidence among men diagnosed with early syphilis in Atlanta, San Francisco, and Los Angeles, 2004 to 2005. J Acquir Immune Defic Syndr 2008; 47:234.
  14. Centers for Disease Control and Prevention (CDC). Outbreak of syphilis among men who have sex with men--Southern California, 2000. MMWR Morb Mortal Wkly Rep 2001; 50:117.
  15. Centers for Disease Control and Prevention (CDC). Primary and secondary syphilis among men who have sex with men--New York City, 2001. MMWR Morb Mortal Wkly Rep 2002; 51:853.
  16. Chen SY, Gibson S, Katz MH, et al. Continuing increases in sexual risk behavior and sexually transmitted diseases among men who have sex with men: San Francisco, Calif, 1999-2001, USA. Am J Public Health 2002; 92:1387.
  17. Su JR, Weinstock H. Epidemiology of co-infection with HIV and syphilis in 34 states, United States—2009. In: proceedings of the 2011 National HIV Prevention Conference, August 13–17, 2011, Atlanta, GA.
  18. Pathela P, Braunstein S, Shepard CS. Population-based HIV incidence among men diagnosed with infectious syphilis, 2000–2011. In: proceedings of the STI&AIDS World Congress 2013, July 14–17, 2013, Vienna, Austria.
  19. Centers for Disease Control and Prevention (CDC). Notes from the field: repeat syphilis infection and HIV coinfection among men who have sex with men--Baltimore, Maryland, 2010-2011. MMWR Morb Mortal Wkly Rep 2013; 62:649.
  20. Solomon MM, Mayer KH, Glidden DV, et al. Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial. Clin Infect Dis 2014; 59:1020.
  21. Mwapasa V, Rogerson SJ, Kwiek JJ, et al. Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi. AIDS 2006; 20:1869.
  22. Reynolds SJ, Risbud AR, Shepherd ME, et al. High rates of syphilis among STI patients are contributing to the spread of HIV-1 in India. Sex Transm Infect 2006; 82:121.
  23. Spielmann N, Münstermann D, Hagedorn HJ, et al. Time trends of syphilis and HSV-2 co-infection among men who have sex with men in the German HIV-1 seroconverter cohort from 1996-2007. Sex Transm Infect 2010; 86:331.
  24. Palacios R, Jiménez-Oñate F, Aguilar M, et al. Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients. J Acquir Immune Defic Syndr 2007; 44:356.
  25. Sadiq ST, McSorley J, Copas AJ, et al. The effects of early syphilis on CD4 counts and HIV-1 RNA viral loads in blood and semen. Sex Transm Infect 2005; 81:380.
  26. Buchacz K, Patel P, Taylor M, et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. AIDS 2004; 18:2075.
  27. Kofoed K, Gerstoft J, Mathiesen LR, Benfield T. Syphilis and human immunodeficiency virus (HIV)-1 coinfection: influence on CD4 T-cell count, HIV-1 viral load, and treatment response. Sex Transm Dis 2006; 33:143.
  28. Jarzebowski W, Caumes E, Dupin N, et al. Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort. Arch Intern Med 2012; 172:1237.
  29. de Almeida SM, Bhatt A, Riggs PK, et al. Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis. J Neurovirol 2010; 16:6.
  30. Weintrob AC, Gu W, Qin J, et al. Syphilis co-infection does not affect HIV disease progression. Int J STD AIDS 2010; 21:57.
  31. Rompalo AM, Joesoef MR, O'Donnell JA, et al. Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study. Sex Transm Dis 2001; 28:158.
  32. Rompalo AM, Lawlor J, Seaman P, et al. Modification of syphilitic genital ulcer manifestations by coexistent HIV infection. Sex Transm Dis 2001; 28:448.
  33. Schöfer H, Imhof M, Thoma-Greber E, et al. Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG). Genitourin Med 1996; 72:176.
  34. Zellan J, Augenbraun M. Syphilis in the HIV-infected patient: an update on epidemiology, diagnosis, and management. Curr HIV/AIDS Rep 2004; 1:142.
  35. French P. Syphilis. BMJ 2007; 334:143.
  36. Zetola NM, Engelman J, Jensen TP, Klausner JD. Syphilis in the United States: an update for clinicians with an emphasis on HIV coinfection. Mayo Clin Proc 2007; 82:1091.
  37. Sands M, Markus A. Lues maligna, or ulceronodular syphilis, in a man infected with human immunodeficiency virus: case report and review. Clin Infect Dis 1995; 20:387.
  38. Yanagisawa N, Imamura A. HIV-positive man with ulceronecrotic skin lesions. Clin Infect Dis 2008; 47:1068.
  39. Tucker JD, Shah S, Jarell AD, et al. Lues maligna in early HIV infection case report and review of the literature. Sex Transm Dis 2009; 36:512.
  40. D'Amico R, Zalusky R. A case of lues maligna in a patient with acquired immunodeficiency syndrome (AIDS). Scand J Infect Dis 2005; 37:697.
  41. Hutchinson CM, Rompalo AM, Reichart CA, Hook EW 3rd. Characteristics of patients with syphilis attending Baltimore STD clinics. Multiple high-risk subgroups and interactions with human immunodeficiency virus infection. Arch Intern Med 1991; 151:511.
  42. Rolfs RT, Joesoef MR, Hendershot EF, et al. 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 1997; 337:307.
  43. Kandelaki G, Kapila R, Fernandes H. Destructive osteomyelitis associated with early secondary syphilis in an HIV-positive patient diagnosed by Treponema pallidum DNA polymerase chain reaction. AIDS Patient Care STDS 2007; 21:229.
  44. Colmegna I, Koehler JW, Garry RF, Espinoza LR. Musculoskeletal and autoimmune manifestations of HIV, syphilis and tuberculosis. Curr Opin Rheumatol 2006; 18:88.
  45. Coyne K, Browne R, Anagnostopoulos C, Nwokolo N. Syphilitic periostitis in a newly diagnosed HIV-positive man. Int J STD AIDS 2006; 17:421.
  46. Gaudio PA. Update on ocular syphilis. Curr Opin Ophthalmol 2006; 17:562.
  47. Rutland E, Harindra VK. Syphilis: an important cause of infectious hepatitis. Int J STD AIDS 2010; 21:215.
  48. Biotti D, Bidot S, Mahy S, et al. Ocular syphilis and HIV infection. Sex Transm Dis 2010; 37:41.
  49. Balba GP, Kumar PN, James AN, et al. Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy. Am J Med 2006; 119:448.e21.
  50. Parc CE, Chahed S, Patel SV, Salmon-Ceron D. Manifestations and treatment of ocular syphilis during an epidemic in France. Sex Transm Dis 2007; 34:553.
  51. Weinert LS, Scheffel RS, Zoratto G, et al. Cerebral syphilitic gumma in HIV-infected patients: case report and review. Int J STD AIDS 2008; 19:62.
  52. Hess CW, Rosenfeld SS, Resor SR Jr. Oculomotor nerve palsy as the presenting symptom of gummatous neurosyphilis and human immunodeficiency virus infection: clinical response to treatment. JAMA Neurol 2013; 70:1582.
  53. Musher DM, Hamill RJ, Baughn RE. Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment. Ann Intern Med 1990; 113:872.
  54. Maharajan M, Kumaar GS. Cardiovascular syphilis in HIV infection: a case-control study at the Institute of Sexually Transmitted Diseases, Chennai, India. Sex Transm Infect 2005; 81:361.
  55. Flood JM, Weinstock HS, Guroy ME, et al. Neurosyphilis during the AIDS epidemic, San Francisco, 1985-1992. J Infect Dis 1998; 177:931.
  56. Ghanem KG, Moore RD, Rompalo AM, et al. Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS 2008; 22:1145.
  57. Oette M, Hemker J, Feldt T, et al. Acute syphilitic blindness in an HIV-positive patient. AIDS Patient Care STDS 2005; 19:209.
  58. Lee JP, Koo SH, Jin SY, Kim TH. Experience of meningovascular syphilis in human immunodeficiency virus infected patient. J Korean Neurosurg Soc 2009; 46:413.
  59. Li JZ, Tucker JD, Lobo AM, et al. Ocular syphilis among HIV-infected individuals. Clin Infect Dis 2010; 51:468.
  60. Uglietti A, Antoniazzi E, Pezzotta S, Maserati R. Syphilitic uveitis as presenting feature of HIV infection in elderly patients. AIDS 2007; 21:535.
  61. Shalaby IA, Dunn JP, Semba RD, Jabs DA. Syphilitic uveitis in human immunodeficiency virus-infected patients. Arch Ophthalmol 1997; 115:469.
  62. Lee SB, Kim KS, Lee WK, et al. Ocular syphilis characterised by severe scleritis in a patient infected with HIV. Lancet Infect Dis 2013; 13:994.
  63. Pasricha JM, Read TR, Street AC. Otosyphilis: a cause of hearing loss in adults with HIV. Med J Aust 2010; 193:421.
  64. Centers for Disease Control and Prevention (CDC). Clinical advisory: ocular syphilis in the United States. www.cdc.gov/std/syphilis/clinicaladvisoryos2015.htm (Accessed on November 08, 2016).
  65. Centers for Disease Control and Prevention (CDC). Symptomatic early neurosyphilis among HIV-positive men who have sex with men--four cities, United States, January 2002-June 2004. MMWR Morb Mortal Wkly Rep 2007; 56:625.
  66. Mishra S, Walmsley SL, Loutfy MR, et al. Otosyphilis in HIV-coinfected individuals: a case series from Toronto, Canada. AIDS Patient Care STDS 2008; 22:213.
  67. Kunkel J, Schürmann D, Pleyer U, et al. Ocular syphilis--indicator of previously unknown HIV-infection. J Infect 2009; 58:32.
  68. Tucker JD, Li JZ, Robbins GK, et al. Ocular syphilis among HIV-infected patients: a systematic analysis of the literature. Sex Transm Infect 2011; 87:4.
  69. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
  70. Augenbraun MH, DeHovitz JA, Feldman J, et al. Biological false-positive syphilis test results for women infected with human immunodeficiency virus. Clin Infect Dis 1994; 19:1040.
  71. Rompalo AM, Cannon RO, Quinn TC, Hook EW 3rd. Association of biologic false-positive reactions for syphilis with human immunodeficiency virus infection. J Infect Dis 1992; 165:1124.
  72. Hicks CB, Benson PM, Lupton GP, Tramont EC. Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus (HIV) with Kaposi sarcoma. A diagnostic dilemma. Ann Intern Med 1987; 107:492.
  73. Tikjøb G, Russel M, Petersen CS, et al. Seronegative secondary syphilis in a patient with AIDS: identification of Treponema pallidum in biopsy specimen. J Am Acad Dermatol 1991; 24:506.
  74. Centers for Disease Control and Prevention (CDC), Health Resources and Services Administration, National Institutes of Health, HIV Medicine Association of the Infectious Diseases Society of America. Incorporating HIV prevention into the medical care of persons living with HIV. Recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2003; 52:1.
  75. Marra CM, Maxwell CL, Smith SL, et al. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 2004; 189:369.
  76. Walter T, Lebouche B, Miailhes P, et al. Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients. Clin Infect Dis 2006; 43:787.
  77. Libois A, De Wit S, Poll B, et al. HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis 2007; 34:141.
  78. Ghanem KG, Moore RD, Rompalo AM, et al. Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms. Clin Infect Dis 2009; 48:816.