The clinical manifestations, serologic responses, efficacy of
treatment, and occurrence of complications of syphilis may be
in patients coinfected with human immunodeficiency virus (HIV).
syphilis is a disease with a broad range of manifestations and
course, assessing reports of unusual clinical or lab- oratory
in HIV-coinfected patients is difficult (1). On March 21 and 22,
experts* from academic medical centers and state and local health
departments met at CDC to discuss the diagnosis and treatment of
syphilis in HIV-infected patients. The following recommendations
developed based on these discussions.
DIAGNOSIS OF SYPHILIS IN HIV-INFECTED PATIENTS
Most HIV-infected patients appear to have a normal serologic
to Treponema pallidum infection (2). However, in some HIV-infected
patients with biopsy- confirmed secondary syphilis, both
and treponemal tests for syphilis are negative (3). In addition,
patients infected with both T. pallidum and HIV have had unusually
titers on nontreponemal serologic tests for syphilis (CDC,
data, 1987-88), possibly because of HIV-related polyclonal B-cell
stimulation. The frequency of unusual clinical and laboratory
manifestations of syphilis in patients coinfected with HIV is
Persons with HIV infection acquired through sexual contact or
intravenous (IV)- drug abuse should be tested for syphilis, and all
sexually active persons with syphilis should be tested for HIV
the informed consent of the patient). HIV test results are
important in managing patients with syphilis and, with appropriate
confidentiality safeguards, should be made available to medical
sonnel who care for these patients.
When clinical findings suggest syphilis is present, but
tests are negative, other tests should be used to determine if
is present. These tests include dark-field microscopy and direct
fluorescent antibody for T. pallidum (DFA-TP) staining of lesion
exudate and examination of biopsy tissue using DFA-TP or Steiner
Laboratories should titrate nontreponemal tests to a final
rather than reporting results as greater than an arbitrary cutoff
(e.g.,greater than 1:512). Specific results permit more accurate
determination of response to therapy and also help identify unusual
serologic responses to syphilis.
Neurosyphilis should be considered in the differential diagnosis
neurologic disease in HIV-infected persons.
Consultation should be obtained to evaluate unusual serologic
results in patients suspected of having syphilis or in those being
followed for response to treatment.
TREATMENT AND FOLLOW-UP
Case reports have suggested that treatment failures, including
progression to neurosyphilis, may occur more frequently in patients
coinfected with HIV than in those with syphilis alone (5,6). This
not yet been confirmed, but because an intact cellular immune
is important in the host response to T. pallidum infection (7) and
because HIV infection impairs cellular immune response in some
patients, an increased frequency of treatment failure is plausible.
Recommended treatment schedules for neurosyphilis have included
benzathine penicillin (8), although treatment with benzathine
penicillin in currently recommended dosages does not achieve
treponemicidal antibiotic levels in the cerebrospinal fluid (CSF)
most patients with syphilis, and rare treatment failures have been
No change in therapy for early syphilis for HIV-coinfected
is recommended. However, there is disagreement on this issue, and
authorities have advised CSF examination and/or treatment with a
regimen appropriate for neurosyphilis for all patients coinfected
syphilis and HIV, regardless of the clinical stage of syphilis
all cases, careful follow-up is necessary to assure adequacy of
Serologic testing after treatment for early syphilis is
for all patients, regardless of HIV infection status. In patients
coinfected with HIV, quantitative nontreponemal tests should be
repeated at 1, 2, and 3 months and at 3-month intervals thereafter
until a satisfactory serologic response to treatment occurs. If the
titer does not decrease appropriately (two-dilution decrease by 3
months for primary syphilis or by 6 months for secondary syphilis)
or if a sustained two-dilution or greater increase occurs, the
should be reevaluated to consider the possibility of treatment
or reinfection, and CSF should be examined. Sexually transmitted
disease (STD) clinics and others providing STD treatment should
A CSF examination should precede and guide treatment of
patients with latent syphilis present for longer than 1 year or for
unknown duration. If an examination is not possible, patients
treated for presumed neuro- syphilis.
Benzathine penicillin regimens should not be used to treat
asymptomatic or symptomatic neurosyphilis in HIV-infected patients.
Patients should be treated for at least 10 days with either aqueous
crystalline penicillin G, 2-4 million units IV every 4 hours (12-24
million units each day), or aqueous procaine penicillin G, 2.4
units intramuscularly daily, plus probenecid 500 mg orally 4 times
Reported by: Div of Sexually Transmitted Diseases, Center for
Prevention Svcs; AIDS Program and Sexually Transmitted Diseases
Laboratory Program, Center for Infectious Diseases, CDC.
Editorial Note: The expert consultants also highlighted the
research priorities related to the diagnosis and treatment of
in HIV-coinfected patients:
The effect of HIV infection on initial clinical and laboratory
manifestations of syphilis and on the efficacy of current syphilis
therapy should be prospectively studied.
A surveillance system should be developed to detect
syphilis, especially neurosyphilis, and unusual clinical and
manifestations of syphilis in patients with and without
The importance of CNS involvement in early syphilis should be
determined in patients with and without HIV coinfection.
Better laboratory methods should be developed for detecting T.
pallidum or T. pallidumantigens in CSF, blood, and lesions.
A better animal model of T. pallidum infection is needed to
the effect of immunosuppression on the course of syphilis.
So that the frequency of unusual manifestations of syphilis can be
determined, health-care providers are requested to notify their
epidemiologists of HIV- infected patients who meet one of the
Neurosyphilis confirmed by CSF examination or histopathology;
Negative serologic tests for syphilis (nontreponemal (VDRL, RPR)
treponemal (FTA-ABS, MHA-TP, HATTS) tests) during secondary
diagnosed by dark- field microscopy or histopathology of lesion
The state epidemiologists will forward these reports without
identifiers to the Division of Sexually Transmitted Diseases,
for Prevention Services, CDC.
Beck-Sague CM, Alexander ER, Jaffe HW. Neurosyphilis and HIV
infection (Letter). N Engl J Med 1987;317:1473.
Schultz S, Araneta MRG, Joseph SC. Neurosyphilis and HIV
(Letter). N Engl J Med 1987;317:1474.
Hicks CB, Benson PM, Lupton GP, Tramont EC. Seronegative
syphilis in a patient infected with the human immunodeficiency
(HIV) with Kaposi sarcoma: a diagnostic dilemma. Ann Intern Med
Swisher BL. Modified Steiner procedure for microwave staining of
spirochetes and nonfilamentous bacteria. J Histotechnol
Berry CD, Hooton TM, Collier AC, Lukehart SA. Neurologic relapse
after benzathine penicillin therapy for secondary syphilis in a
with HIV infection. N Engl J Med 1987; 316:1587-9.
Johns DR, Tierney M, Felsenstein D. Alteration in the natural
history of neurosyphilis by concurrent infection with the human
immunodeficiency virus. N Engl J Med 1987; 316:1569-72.
Pavia CS, Folds JD, Baseman JB. Cell-mediated immunity during
syphilis: a review. Br J Vener Dis 1978;54:144-50.
Greene BM, Miller NR, Bynum TE. Failure of penicillin G
in the treatment of neurosyphilis. Arch Intern Med 1980;140:1117-8.
Mohr JA, Griffiths W, Jackson R, Saadah H, Bird P, Riddle J.
Neurosyphilis and penicillin levels in cerebrospinal fluid. JAMA
Cuddy PG. Benzathine penicillin G in the treatment of
neurosyphilis. Drug Intell Clin Pharm 1982;16:205-10.
Tramont EC. Syphilis in the AIDS era. N Engl J Med
Brown ST, Zaidi A, Larsen SA, Reynolds GH. Serological response
syphillis treatment: a new analysis of old data. JAMA
*Expert consultants: M Rein, MD, Univ of Virginia School of
Bolan, MD, San Francisco Dept of Public Health; W Boyd, Georgia
Human Resources; D Burke, Tennessee Dept of Health and Environment;
Greaves, MD, Howard Univ Hospital; V Mesa, MD, Detroit Dept of
E Hook, III, MD, Johns Hopkins Univ School of Medicine; J Hadler,
Connecticut State Dept of Health Svcs; D Des Jarlais, PhD, State of
York Div of Substance Abuse Svcs; S Lukehart, PhD, Univ of
School of Medicine; M Lovett, MD, Univ of California, Los Angeles,
School of Medicine; R Magana, PhD, Orange County (California)
Dept; W McCormack, MD, Downstate Medical Center, Brooklyn, New
Schultz, MD, New York City Dept of Health; E Tramont, MD, Walter
Army Medical Center; H Jaffe, MD, CDC.
**In evaluating biopsy specimens, histologic stains (Warthin Starry
Silver, Steiner) must be interpreted with caution since other
spirochetes and artifacts may be misidentified as T. pallidum with
these silver stains.
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