Risk of Syphilis in MSM Doesn't Decrease With Repeated Episodes

The risk of syphilis doesn’t decrease with repeated episodes of the infection, which may indicate challenges ahead for the development of a vaccine, according to a recent study of HIV-infected men who have sex with men (MSM) in Switzerland.

The prospective cohort study, published in Open Forum Infectious Diseases, included 2513 MSM infected with HIV who received routine syphilis testing from 2004 to 2018 with the goal of determining risk factors for syphilis, which is re-emerging globally.

“In HIV-infected MSM, we observed no indication of decreased syphilis risk with repeated syphilis episodes,” Jan A. Roth, MD, of the Division of Infectious Diseases and Hospital Epidemiology at the University Hospital Basel, told Contagion^®. “The extent of sexual risk behavior over time was the strongest risk factor for repeated syphilis episodes. Our results suggest that vaccine development might be very difficult for syphilis prevention.”

All study participants were negative for syphilis at the beginning of the 14-year study. The data were from the Swiss HIV Cohort Study, which covers about 80% of new HIV infection in Switzerland since 1996 with semi-annual blood collections. More than 80% of syphilis episodes reported were among MSM.

Within the study period, 657 (26.1% of participants had at least 1 syphilis episode, 144 (5.7% had at least 2 episodes, and 42 (1.7%) had 3 or more episodes. Repeated syphilis episodes were more common among young MSM with casual partners and exposure to condomless anal sex.

Risk of syphilis episodes increased most among participants who had occasional sexual partners with or without condomless sex, with crude hazard ratios of 4.99 and 2.54. The number of prior episodes had a 1.15 hazard ratio per 1-episode increase. Being currently on antiretroviral therapy also was associated with increased probability, with a hazard ratio of 1.62.

“The observed association of antiretroviral therapy with repeated syphilis episodes was a surprise and warrants further immunological and epidemiological investigation: It may be a non-causal association,” Roth told Contagion^®.

While the study found no decrease in risk of syphilis with repeated episodes, it was unable to determine whether subsequent episodes resulted in partial attenuation.

“The most important fact is that repeated episodes of syphilis are not rare and that repeated testing/screening, also without symptoms, is essential to discover new episodes,” Roth told Contagion^®. “It is crucial—within the Swiss HIV Cohort Study this is done—to recommend frequent testing for syphilis in MSM. Hence, to implement this knowledge into daily practice.”

The number of syphilis cases climbed 13.3% to more than 115,000 in 2018, according to the US Centers for Disease Control and Prevention.

As sexually transmitted infections rise, investigators are examining risk factors and coinfections. Pre-exposure prophylaxis may play a role, with one study finding a higher incidence of sexually transmitted infections among people starting and persistently using PrEP. Another recent study found that the incidence of the disease is 3-fold higher among patients with end-stage renal disease than those of the general population.