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Researchers link increase in syphilis cases to highly active ART
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Canadian researchers have suggested that a substantial increase in syphilis cases in recent years primarily affecting HIV-positive men who have sex with men may be linked to a reduced immune response to syphilis caused by highly active ART.
Michael L. Rekart, MD, DTM&H, MHSc, clinical professor of Medicine and Global Health at the University of British Columbia, and colleagues, reported that cases of infectious syphilis increased 90.6% in British Columbia, Canada, from 2005 to 2014, with men who have sex with men (MSM) accounting for 88.9% of cases in 2014. It is suspected that the effectiveness of highly active ART (HAART) led to the perception among both HIV-infected and HIV-uninfected individuals that transmission is less likely to occur, contributing to a rise in sexual risk taking, especially unprotected anal intercourse. This is expected to increase the incidence of nonHIV sexually transmitted infections (STIs), according to the researchers. However, although there was a 235% increase in syphilis among men, there was a much smaller increase in chlamydia (56.9%) and gonorrhea (42.1%). Larger increases in syphilis were also reported in the United States during this period, the researchers said.
“Since rising syphilis incidence appears to have outpaced gonorrhea and chlamydia, predominately affecting HIV-1 positive MSM, behavioral factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence,” they wrote in Sexually Transmitted Infections. “HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to [Treponema pallidum]. This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications.”
To test their theory, Rekart and colleagues developed a mathematical model to predict rates of syphilis. They investigated the effects of HAART-related behavior and immunology, assuming that individuals receiving HAART adopted riskier sexual behaviors and had a higher susceptibility to T. pallidum than untreated individuals.
The simulation results showed that risky sexual behavior as the sole cause of increased syphilis rates did not correspond with the actual current rates of syphilis. However, when considering both behavior changes and immunity effects, the rate was estimated to be similar to the current incidence rate of syphilis in British Columbia and several other countries, according to a press release.
Despite these findings, Rekart warned that it is vital for HIV patients to continue receiving HAART.
“HAART drugs are live-saving; syphilis is curable,” he said in the release. “HAART drugs bring people with HIV back to a normal state of immunity, they can have a normal life, they don’t get most opportunistic infections such as tuberculosis.”
The researchers suggested that the depletion of CD4+ memory T cells in HIV-infected patients may enhance their susceptibility to syphilis reinfection. In addition, an upregulation of CCR5 receptors by treponemal lipoproteins may boost the susceptibility of monocytes to HIV infection, further weakening immune responses to T. pallidum.
“We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed,” Rekart and colleagues concluded. “If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such as T. pallidum.”
In a related editorial, Khalil Georges Ghanem, MD, PhD, deputy director of education and associate professor of medicine at Johns Hopkins University, Bayview Medical Center, and colleagues identified several limitations of the study. The authors noted that the increase in syphilis rates compared with other STIs may reflect inadequate screening, and that there have been STI outbreaks involving individuals not receiving ART in regions where syphilis is more pronounced than gonorrhea and chlamydia. In addition, they stated that the dynamics of HAART-related behavior may be too complicated to accurately capture in the model, and there is a lack of sensitivity analyses validating their results.
“Despite these limitations, the hypothesis is intriguing and warrants careful consideration,” Ghanem and colleagues wrote. “We are living in an era where ART is being used to effectively treat and prevent HIV infection. To some extent, this seems to have tempered the urgency to control other STDs. As history has shown many times over, that would be a costly mistake.
“If further investigations support a role for ART in increasing susceptibility to syphilis, this will provide one more reason why screening, diagnosis and treatment of STIs in MSM must be prioritized.” – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.
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