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Syphilis has been a persistent public health challenge for centuries, and is now gaining renewed attention against the backdrop of the HIV pandemic. Recent reports indicate that syphilis incidence is rising in the U.S.,1, 2 leading some epidemiologists to suspect that similar increases in HIV infection may not be far behind. Syphilis infection significantly increases susceptibility to HIV infection. For its part, HIV can alter the clinical course of syphilis, increase the likelihood of relapse, and confound the diagnosis of neurosyphilis. Treatment of syphilis in coinfected patients is complicated, and success may depend on the integrity of host immune response as much as it does on antibiotic effect. This article reviews the current litera…