Interpretation of serologic tests should be the same for HIV-positive and HIV-negative individuals. Because syphilis has variable clinical manifestations and an unpredictable course, evaluation of case reports of unusual clinical or laboratory manifestations of syphilis in HIV-infected patients is difficult. Although unusual serologic responses have been reported in HIV-positive patients, including high titers of nontreponemal tests, delayed appearance of positive titers, and false-negative tests, most HIV-positive patients respond serologically in somewhat the same way as noninfected patients. Some recommend that all HIV-positive men be screened twice a year by RPR or VDRL to identify latent disease and to appropriately stage individuals. By establishing a serologic history, unnecessary lumbar punctures required for latent syphilis of unknown duration can be avoided. Because of concerns about false-negative serologic tests or a delayed immunologic response, if the diagnosis of syphilis is suggested on clinical grounds but reagin tests are negative, alternative tests should be performed. These tests include darkfield examination of lesions and direct fluorescent antibody staining for T pallidum of lesion exudate or biopsy specimens.

The diagnosis of neurosyphilis in HIV-infected patients is complicated by the fact that cerebrospinal fluid abnormalities are frequently seen and may be due to neurosyphilis or HIV infection itself. The significance of these abnormalities is unknown, and similar abnormalities are frequently seen in non-HIV-infected patients with primary or secondary syphilis. Despite occasional reports of HIV-infected patients who progress to develop neurosyphilis despite appropriate therapy for early disease, the vast majority of HIV-infected patients with primary or secondary syphilis respond appropriately to currently recommended regimens. Thus, although some recommend a cerebrospinal fluid examination for all HIV-positive patients with syphilis, such testing is probably not needed in those with early disease. In contrast, a lumbar puncture should be performed in HIV-positive patients if they have late latent syphilis or syphilis of unknown duration, if neurologic signs are present, or if they have failed therapy. A recent study found that HIV-positive patients with a nontreponemal antibody titer ? 1:32 had a sixfold increased risk of having neurosyphilis, and if the CD4 count was ? 350/mcL there was a threefold increased risk of neurosyphilis, suggesting that these subgroups should also undergo lumbar puncture. Following treatment, cerebrospinal fluid white blood cell counts normalize within 12 months regardless of HIV status, while the cerebrospinal fluid VDRL is slower to normalize in HIV-infected individuals, especially those with CD4 counts < 200 cells/mcL. As discussed above, the same criteria for failure apply to HIV-positive and HIV-negative patients, and retreatment regimens are the same.

Treatment of HIV-positive patients with primary and secondary syphilis is the same as for HIV-negative patients. Because of concerns about the adequacy of this therapy, some experts recommend additional therapy with 2.4 million units of benzathine penicillin intramuscularly weekly for 3 weeks instead of single-dose therapy. Because of ongoing concerns about adequacy of therapy, careful clinical and serologic follow-up should be done at 3, 6, 9, 12, and 24 months.

HIV-infected patients with late latent syphilis, syphilis of unknown duration, and neurosyphilis should be treated like HIV-negative individuals, with follow-up at 6, 12, 18, and 24 months.

Because clinical experience in treating HIV-infected patients with syphilis is based on penicillin regimens, few options exist for treating the penicillin-allergic patient. For primary, secondary, and early latent syphilis, doxycycline or tetracycline regimens can be used. For late latent syphilis, latent syphilis of unknown duration, and neurosyphilis, penicillin regimens should be used even if this requires skin testing and desensitization.