Background Cohort and cross-sectional studies have shown syphilis is associated with risk for HIV infection. However, population-based estimates of the actual risk for HIV following syphilis infections are lacking.

Methods In New York City, HIV and STD surveillance registries are separately maintained. Cases reported to these registries with diagnoses from 2000-June 2010 were matched using a deterministic algorithm. We measured HIV incidence among men following primary or secondary syphilis diagnoses. We calculated time at risk for HIV among men diagnosed with HIV ≥ 60 days after syphilis diagnosis; men without reported HIV were presumed uninfected and censored on 3/31/2011.

Results Of 2,805 men with syphilis who contributed 11,714 person-years of follow-up, 423 (15.1%) subsequently acquired HIV; annual incidence was 3.61% (95% CI: 3.27%, 3.97%). Median time to HIV diagnosis was 582 days (range 60–3150). HIV incidence was highest among men who have sex with men (MSM) (5.56%, 95% CI: 5.02%–6.13%), relatively uniform across race/ethnicity and year of syphilis diagnosis, and decreased with increasing age at syphilis diagnosis. HIV incidence was higher among males with secondary compared with primary syphilis (4.10% vs. 2.64%, p < 0.0001). HIV incidence among males with syphilis who were diagnosed with another bacterial STD before HIV (14% of cases) was over double the incidence among those who were concurrently diagnosed (7.89% vs. 3.44%, p = 0.002) or reported only with syphilis (7.89% vs. 2.89%, p < 0.0001) during the analytic period.

Conclusions On a population level, one in 20 MSM with syphilis are diagnosed with HIV within a year; highly frequent HIV testing and HIV pre-exposure prophylaxis should be considered for HIV-negative syphilis cases. Secondary syphilis suggests untreated primary lesions; the higher HIV incidence among these cases underscores the importance of appropriate STD/HIV screening and early syphilis detection. Registry matching/integration permits identification of high-risk individuals, such as men repeatedly acquiring STD, for targeting prevention activities.