Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment

Ann Intern Med. 1990 Dec 1;113(11):872-81. doi: 10.7326/0003-4819-113-11-872.


Purpose: To evaluate evidence that concurrent infection with human immunodeficiency virus (HIV) alters both the natural history of syphilis (by increasing the frequency of early neurosyphilis) and the response to penicillin.

Data identification: Review of major works on syphilis in the English language and files maintained since 1971, supplemented by a systematic search using Index Medicus and MEDLARS.

Data extraction: The works mentioned above were critically reviewed for information on early neurosyphilis and, where relevant, HIV infection.

Results of data analysis: The central nervous system is regularly involved in early syphilis. Standard recommended doses of benzathine penicillin provide cerebrospinal fluid levels that are probably at the borderline of efficacy, and cure relies on treatment and an adequate host immune response. Early neurosyphilis, appearing within 2 years of onset of infection with Treponema pallidum, was uncommon in the prepenicillin era and usually occurred after inadequate therapy. This complication was exceedingly rare in the first three decades of penicillin use. In contrast, in the past decade, 40 patients with HIV infection have been reported to have asymptomatic neurosyphilis, or syphilitic meningitis, cranial nerve abnormalities (predominantly in cranial nerves II and VIII), or cerebrovascular accidents, singly or together. In 40% of cases, HIV infection was first diagnosed when neurologic symptoms appeared. Of the 38 patients for whom information was available, 18 had the acquired immunodeficiency syndrome (AIDS), 7 had AIDS-related complex, and 13 had antibody to HIV. Sixteen had previously been treated for syphilis, of whom 5 (31%) had received benzathine penicillin within the previous 6 months. Preliminary data also suggest that skin lesions and VDRL (Venereal Disease Research Laboratory) antibody in HIV-infected patients with secondary syphilis respond more slowly to conventional penicillin therapy.

Conclusion: Intensive therapy and follow-up observation is indicated for early syphilis in HIV-infected subjects. Novel approaches to treatment deserve systematic evaluation.

Publication types

  • Review

MeSH terms

  • HIV Infections / complications*
  • Humans
  • Neurosyphilis / complications
  • Neurosyphilis / physiopathology
  • Penicillins / therapeutic use
  • Syphilis / complications*
  • Syphilis / drug therapy
  • Syphilis / physiopathology
  • Syphilis Serodiagnosis


  • Penicillins