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  19th Conference on Retroviruses and
Opportunistic Infections
Seattle, WA March 5 - 8, 2012
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Antiretrovirals May Cut Neurosyphilis Risk and Improve Response to Neurosyphilis Therapy
  19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
HIV-positive people not taking antiretroviral therapy (ART) had a twice higher risk of neurosyphilis than those on ART, according to results of a 519-person study [1]. And antiretroviral-treated people responded to neurosyphilis therapy faster than those not taking antiretrovirals. Antiretroviral central nervous system (CNS) penetration did not influence either finding.
In the United States and Europe syphilis rates rose dramatically in HIV-positive people--usually men who have sex with men (MSM)--with the advent of triple antiretroviral therapy in the late 1990s. Several studies found that neurosyphilis is more common in HIV-positive people with a serum rapid plasma reagin (RPR) titer at or above 1:32 and a CD4 count at or below 350 [2-4]. And some work suggests that neurosyphilis is more common in people not on ART [5], the hypothesis explored in this study of HIV-positive people with syphilis in Seattle, Washington [1].
Christine Marra and University of Washington colleagues reported that these 519 people with syphilis all had a neurologic exam and underwent lumbar puncture and venipuncture. The group included 133 people (26%) treated for neurosyphilis who had follow-up 3, 6, and 12 months after neurosyphilis therapy.
Median age was similar in the overall group and the neurosyphilis group (39 and 38), and 97% in both groups were MSM. Prevalence of early versus late-stage syphilis was 76% in the overall group and 74% in the neurosyphilis group. Respective serum RPR titers were 1:64 and 1:128. Median CD4 count and viral load were 424 and 401 and 3.24 and 4.29 log10 copies/mL in the overall group and the neurosyphilis group. While 53% in the overall group were on ART, only 32% in the neurosyphilis group were taking antiretrovirals.
Multivariate analysis considering ART status, RPR titer, syphilis stage, and year of syphilis diagnosis determined that not taking ART and three other factors independently raised the risk of symptomatic neurosyphilis or neurosyphilis defined as a reactive cerebrospinal fluid (CSF) VDRL test, at the following odds ratios (OR) (and 95% confidence intervals):
Off ART:
Symptomatic neurosyphilis: OR 2.4 (1.4 to 4.2), P < 0.01
Reactive CSF-VDRL: OR 2.1 (1.2 to 3.7), P < 0.01)
RPR titer at or above 1:32:
Symptomatic neurosyphilis: OR 3.3 (1.5 to 7.2), P < 0.01
Reactive CSF-VDRL: OR 10.1 (3.7 to 27.1), P < 0.001
Late-stage syphilis:
Reactive CSF-VDRL: OR 3.0 (1.6 to 5.6), P < 0.001
Syphilis diagnosed before 2006:
Reactive CSF-VDRL: OR 1.7 (1.0 to 3.1), P = 0.05
Among people on ART, antiretroviral CNS penetration score did not affect risk of neurosyphilis.
Among people with a reactive CSF-VDRL, the white blood cell count in CSF normalized significantly more quickly with neurosyphilis therapy in those taking ART than in those off ART (P = 0.001). Antiretroviral CNS penetration score did not affect this result.
Marra and colleagues believe their findings "suggest that host immune status is an important determinant of the course of syphilis and neurosyphilis in HIV-infected patients."

1. Marra C, Ho E, Tantalo L, Sahi S, Dunaway S, Jones T, Lukehart S. ARV use decreases neurosyphilis risk and improves response to neurosyphilis therapy. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 486. http://www.retroconference.org/2012b/PDFs/486.pdf.
2. Marra CM, Maxwell CL, Smith SL, et al. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis. 2004;189:369-376. http://jid.oxfordjournals.org/content/189/3/369.long.
3. Libois A, De Wit S, Poll B, et al. HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis. 2007;34:141-144.
4. Ghanem KG, Moore RD, Rompalo AM, et al. Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms. Clin Infect Dis. 2009;48:816-821. Erratum in Clin Infect Dis. 2009;48:1491. http://cid.oxfordjournals.org/content/48/6/816.long.
5. Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA. Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS. 200;22:1145-1151. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553365/?tool=pubmed.