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 Jul 31;337(5):307-14. doi: 10.1056/NEJM199707313370504.


Background: Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus (HIV) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis.

Methods: In a multicenter, randomized, double-blind trial, we assessed two treatments for early syphilis: 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid. The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up.

Results: From 1991 through 1994, 541 patients were enrolled, including 101 patients (19 percent) who had HIV infection but differed little from the uninfected patients in their clinical presentations. The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status. Serologically defined treatment failures were more common among the HIV-infected patients. The single clinically defined treatment failure was in an HIV-infected patient. Rates of serologically defined treatment failure did not differ according to treatment group (18 percent at six months with usual therapy; 17 percent with enhanced therapy). T. pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients (24 percent) and after therapy in 7 of 35 patients tested. None had clinically evident neurosyphilis, and the rate of detection of T. pallidum did not differ according to HIV status.

Conclusions: After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection, but clinically defined failure was uncommon in both groups. Enhanced treatment with amoxicillin and probenecid did not improve the outcomes. Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested, such a finding did not predict treatment failure. The current recommendations for treating early syphilis appear adequate for most patients, whether or not they have HIV infection.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amoxicillin / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination / therapeutic use*
  • Female
  • HIV Infections / complications*
  • Humans
  • Male
  • Penicillin G Benzathine / therapeutic use*
  • Penicillins / therapeutic use*
  • Probenecid / therapeutic use*
  • Syphilis / complications
  • Syphilis / drug therapy*
  • Syphilis Serodiagnosis
  • Treatment Failure
  • Treponema pallidum / isolation & purification


  • Penicillins
  • Amoxicillin
  • Probenecid
  • Penicillin G Benzathine