CSF abnormalities less likely to normalise in HIV-positive patients treated for neurosyphilis

Michael Carter
Published: 23 March 2004

A key laboratory marker used to measure the success of antibiotic treatment for neurosyphilis is significantly more likely to be abnormal in HIV-positive individuals, particularly those with a low CD4 cell count, than in patients who do not have HIV, according to research published in the April 1st edition of Clinical Infectious Diseases, which is now available on-line. The investigators describe this as “concerning” and raise the possibility that HIV-positive individuals, particularly those with severely impaired immunity, require more intensive treatment for neurosyphilis. However, an editorial accompanying the article asserts that the normalisation of other markers used to test the success of neurosyphilis therapy indicates disease inactivity and that HIV-positive patients do not need more intensive treatment.

US treatment guidelines recommend that neurosyphilis be treated with one of two injected antibiotic regimens: high dose intravenous penicillin G, or intramuscular penicillin G plus probenecid penicillin. For HIV-positive individuals, intravenous ceftriaxone is an acceptable treatment.

It is not possible to culture syphilis, so the success of treatment for neurosyphils is assessed by looking at three laboratory markers. US treatment guidelines state that white blood cells in the cerebrospinal fluid (CSF) should normalise six months after the completion of antibiotic treatment, as should CDF protein, CSF Venereal Disease Laboratory (VDRL) reactivity and serum titers.

Investigators from eight US universities wished to see if the currently used antibiotic regimens were effective in a study population of 59. The overwhelming majority were men (56, 94%), and of these 46 (78%) were HIV-positive. All the patients were treated with one of the three regimens mentioned above.

The median duration of follow-up was 6.9 months, and all patients had a lumbar puncture to obtain CSF to assess the success of treatment at three months. Individuals with abnormalities at this stage had further lumbar punctures performed at six and twelve months. Blood samples to test for plasma titers were obtained at months three, six and twelve after the completion of treatment.

The three treatment regimens were found to be equally effective. White blood cells normalised in all patients within a median of 3.8 months, protein concentration within a median of 4.8 months, CSF-VDRL within in a median of 3.9 months and blood titers within a median of 4.4 months after the completion of treatment.

However ,the investigators found that CSF-VDRL reactivity was less likely to normalise in HIV-positive individuals than in HIV-negative patients (p=0.03). Furthermore, HIV-positive patients whose CD4 cell count was below 200 cells/mm3 were even less likely to experience a normalisation in their CSF-VDRL than were HIV-negative individuals (HR 3.7; 95% CI, 1.2 – 11.2; p=0.02).

The investigators comment, “HIV-infected subjects were 2.5 times less likely to normalise CSF-VDRL reactivity, even after taking into account baseline CSF-VDRL titers and stage of syphilis when neurosyphilis was diagnosed.” They also noted that HIV-positive patients with low CD4 cell counts were even less likely to experience a normalisation in CSF-VDRL, suggesting that “HIV-induced immune impairment contributes to the slower normalisation… and may support the contention…that clearance of [central nervous system] organisms can be impaired by HIV infection.”

Although the investigators admit that they do not know if this decreased likelihood of CSF-VDRL normalisation is equivalent to treatment failure, they state that their findings are “concerning” and raises the question whether HIV-positive individuals, particularly those with a CD4 cell count, require more intensive treatment for neurosyphilis.

An editorial accompanying the article, however, maintains that the normalisation in CSF white blood cell count “documents disease inactivity and does not require re-treatment, even when the results of CSF-VDRLs are persistently positive.” The author concludes that follow-up of the patients in the study should provide a definitive answer.

Further information on this website

Syphilis - overview

Syphilis - factsheet


Marra MC et al. Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter?. Clinical Infectious Diseases 38 (on-line edition), 2004.

Simon R et al. The great pox. Clinical Infectious Diseases 38 (on-line edition), 2004.

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