• Arlene C Seña, Xiao-Hui Zhang, Trudy Li, He-Ping Zheng, Bin Yang, Li-Gang Yang, Juan C Salazar, Myron S Cohen, M Anthony Moody, Justin D Radolf, and Joseph D Tucker.
• Department of Medicine, Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. idrod@med.unc.edu.
• Bmc Infect Dis. 2015 Oct 28; 15: 479.

BackgroundSyphilis remains a global public health threat and can lead to severe complications. In addition to resolution of clinical manifestations, a reduction in nontreponemal antibody titers after treatment is regarded as "proof of cure." However, some patients manifest < 4-fold decline ("serological non-response") or persistently positive nontreponemal titers despite an appropriate decline ("serofast") that may represent treatment failure, reinfection, or a benign immune response. To delineate these treatment phenomena, we conducted a systematic review of the literature regarding serological outcomes and associated factors among HIV-infected and -uninfected subjects.MethodsSix databases (PubMed, Embase, CINAHL, Web of Science, Scopus, and BIOSIS) were searched with no date restrictions. Relevant articles that evaluated serological treatment responses and correlates of serological cure (≥ four-fold decline in nontreponemal titers) were included.ResultsWe identified 1693 reports in the literature, of which 20 studies met selection criteria. The median proportion of patients who had serological non-response was 12.1% overall (interquartile range, 4.9-25.6), but varied depending on the time points after therapy. The serofast proportion could only be estimated from 2 studies, which ranged from 35.2-44.4%. Serological cure was primarily associated with younger age, higher baseline nontreponemal titers, and earlier syphilis stage. The relationship between serological cure and HIV status was inconsistent; among HIV-infected patients, CD4 count and HIV viral load was not associated with serological cure.ConclusionsSerological non-response and the serofast state are common syphilis treatment outcomes, highlighting the importance of determining the immunological and clinical significance of persistent nontreponemal antibody titers after therapy.

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