Syphilis and HIV — The Story Continues



In a trial of pre-exposure prophylaxis among men who have sex with men, syphilis infection was associated with acquisition of HIV.


A link between syphilis and HIV infection has been noted since the early days of the HIV pandemic, with consistently higher HIV rates among patients with syphilis in retrospective cohort studies. The Pre-exposure Prophylaxis Initiative (iPrEx) trial offered an opportunity to prospectively assess the relation between prevalent and incident syphilis and acquisition of HIV infection in a closed cohort of HIV-seronegative men who have sex with men (MSM).

At the time of screening, 333 of 2499 participants (13.3%) were found to have prevalent syphilis based on reactive syphilis serology (rapid plasma reagin or Venereal Disease Research Laboratory positivity, plus fluorescent treponemal antibody-absorption confirmation). The rate of incident syphilis diagnosis during the trial was 7.3 cases per 100 person-years of follow-up, with no difference between the active drug (tenofovir/FTC) and placebo groups.

A total of 129 incident HIV infections were diagnosed during the trial, and the new HIV infection rate was significantly higher among participants with incident syphilis than among those without (8.0 vs. 2.8 cases per 100 person-years; hazard ratio, 2.6; 95% confidence interval, 1.6–4.4). In multivariable analysis, the difference remained significant after controlling for other predictors of HIV and sexually transmitted infections. The presence of syphilis did not attenuate the efficacy of pre-exposure prophylaxis (PrEP), and PrEP use had no effect on the association between incident syphilis and incident HIV infection.


The ongoing syphilis epidemic in the U.S. disproportionately affects MSM, and syphilis is likely playing a major role in the continued transmission of HIV in this population. With the new emphasis on PrEP as part of the overall strategy to reduce the number of new HIV infections, targeting individuals with newly diagnosed syphilis for PrEP programs seems like a good initial strategy.

Note to readers: At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


  1. Solomon MM et al. Syphilis predicts HIV incidence among men and transgender women who have sex with men in a pre-exposure prophylaxis trial. Clin Infect Dis 2014 Jun 13; [e-pub ahead of print]. (

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