Significant relationship between viral load and neurosyphilis risk

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The overwhelming majority of early syphilis cases in patients with HIV in Warsaw had neurological involvement, Polish investigators report. There was a significant relationship between HIV viral load and the risk of neurosyphilis.

Lumbar puncture was used to diagnose neurosyphils, but because this procedure is unpopular with patients and involves risks, the investigators recommend that all HIV-positive patients diagnosed with early syphilis should receive antibiotic therapy that has good penetration into the central nervous system (CNS).

Incidence of the sexually transmitted infection syphilis is high among patients with HIV, most especially among men who have sex with men (MSM), and incidence has risen since 2000. European guidelines for the management of syphilis suggest that patients with HIV may have an increased risk of early neurosyphilis and that this may be asymptomatic.

Neurosyphilis is of especial concern for individuals with HIV as it could exacerbate the cognitive decline that has been associated with HIV infection in some research. A recent report found a relationship between neurosyphilis and HIV viral load in cerebrospinal fluid (CSF), whereas another identified a link between viral load and subsequent cognitive decline.

Guidelines recommend that patients with high syphilis titres (1/32) should be investigated for neurosyphilis.

With these research findings and guidelines in mind, Polish investigators designed a prospective study to assess the frequency of neurosyphilis among HIV-positive patients diagnosed with early syphilis and to assess the association between neurosyphilis and HIV-related factors, such as CD4 cell count, HIV viral load and treatment with antiretroviral therapy (treatment vs. no treatment).

Recruitment took place between 2008 and 2012 at an outpatient clinic in Warsaw. During this time, 191 HIV-positive individuals were diagnosed with early syphilis. Of these, 93% has high syphilis titres. Neurological examination using lumbar puncture was offered to all patients but only 59 (33%) consented. A further 13 patients with low titres and symptoms of neurosyphilis were also recruited to the study.

All 72 patients were male, their median age was 33 years and 89% were MSM. Just over half the patients (51%) were taking HIV therapy at the time syphilis was diagnosed. Median CD4 cell count and viral load were 521 cells/mm3 and 24,500 copies/ml, respectively. Lumbar puncture confirmed neurosyphilis in 90% of patients.

No relationship was found between neurosyphilis risk and CD4 cell count. However, among patients with neurological involvement, there was a significant relationship between pleocytosis – increased white blood count – and serum viral load above 1000 copies/ml (p = 0.045). Neurosyphilis was also significantly associated the absence of HIV therapy (p = 0.0328).

Patients with confirmed neurosyphilis were treated with antibiotic therapy with good CNS penetration.

“A very high proportion of confirmed neurosyphilis seen in patients with relatively low serum…titres may suggest that CNS involvement should be suspected regardless of…titre,” conclude the authors. £Taking into account updated indications and risks associated with lumbar puncture, it may be preferable to use treatments with good CNS penetration in all HIV-positive patients diagnosed with syphilis.”

Abstract
Background
Syphilis is an infection frequently seen with HIV, and European guidelines on the management of syphilis suggest that HIV-infected patients may have an increased risk of early neurological involvement, sometimes asymptomatic. Recent study shows a relationship between neurosyphilis and cerebrospinal fluid (CSF) HIV viral load (VL), which in turn may be associated with subsequent neurocognitive decline.
Objectives and methods
The aim of the study was estimation of the frequency of neurosyphilis among HIV-positive patients with early syphilis. The study included all patients diagnosed with early syphilis who had lumbar puncture performed in the years 2008–2012. Analysis included CSF parameters (serology, mononuclear cells, protein, glucose, chloride and lactate levels), CD4 count, serum VL and highly active antiretroviral therapy (HAART). Diagnosis of neurosyphilis was confirmed by CSF serology [positive fluorescent treponemal antibody and/or Venereal Disease Research Laboratory (VDRL) test(s)] and increased number of mononuclear cells. Statistical analysis included χ2 tests with an accepted significance level of P < 0.05. Results Lumbar puncture was performed in 72 patients, all men, with median age 33 (interquartile range 11) years. Neurosyphilis was confirmed in 65 (90.28%) of the patients. No statistically significant association between CSF parameters and CD4 count was found. However, statistically significant associations were found only between pleocytosis and serum VL > 1000 HIV-1 RNA copies/mL (P = 0.0451), as well as HAART treatment (P = 0.0328). The proportion of confirmed neurosyphilis cases, also in patients with low serum VDRL titres, was very high.
Conclusions
Considering the high proportion of patients who objected to having LP performed in the absence of neurological symptoms and the risk associated with this procedure, it may be preferable to use treatments with good CNS penetration in all HIV-positive patients with early syphilis.

Aidsmap material
HIV Medicine abstract


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