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HIV Treatment May Be Behind Rising Syphilis Rates Among Gay Men

February 9, 2017

HIV-positive individuals on antiretroviral therapy, and HIV-negative individuals on pre-exposure prophylaxis (PrEP), may be at higher risk of contracting syphilis, which could help explain the rise in syphilis rates among men who have sex with men (MSM), according to a new study.

Syphilis, once on the verge of elimination, has been on the rise for the more than a decade mostly in MSM. The prevailing theory in public health has been that this is the result of a change in behavior: That MSM are having more unprotected sex because they are less concerned about contracting HIV or dying from AIDS-related illnesses in this era of antiretroviral therapy, PrEP, and undetectable viral counts.

Researchers in Canada and South Africa, however, questioned this theory, noting that rates of other sexually transmitted infections (STIs), such as chlamydia and gonorrhea, are not rising as rapidly in the same population. Instead, they speculated that there might be a biological reason why MSM -- many of whom are HIV-positive and on highly active antiretroviral therapy (HAART) -- are becoming infected with syphilis. Their new study, published in the journal Sexually Transmitted Infections, uses mathematical modeling to test this hypothesis.

Syphilis is one of the older STIs, with an outbreak among French soldiers recorded in the late 1400s. Caused by the bacterium, Treponema pallidum, it goes through three main stages.

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Related: What's Next for STIs in MSM?

The first or primary stage of syphilis usually appears as small, hard sores, called chancres. These sores are painless and tend to go away with or without treatment. If not discovered and treated, the infection can progress to the secondary stage, which often starts with a rash covering some or all of the body. Like the original sores, the rash can clear up on its own. Other symptoms in the secondary stage may include fever, swollen lymph glands, sore throat, hair loss, headaches, weight loss, muscle aches and fatigue. Syphilis is easy to cure with antibiotics in the primary or secondary phase. Unfortunately, these symptoms are often mistaken for other common illnesses such as the flu, and the infection is not diagnosed.

If left untreated, syphilis can enter the latent stage in which it can damage the internal organs, including the brain, nerves, eyes, heart, blood vessels, liver, bones and joints. Symptoms of the late stage include difficulties coordinating muscle movements, paralysis, numbness, gradual blindness and dementia.

Rates of syphilis have been steadily increasing since at least 2000 when there were only 6,103 cases of primary and secondary (P&S) syphilis reported. By 2015, there were 23,872 cases of P&S syphilis reported. Most of these cases are among MSM. In 2015, MSM accounted for 60% of cases -- 54% were in men who only had sex with men and 6% were in men who had sex with both men and women. Data from 31 states that same year suggest that 70% of those diagnosed with P&S syphilis were also HIV-positive.

As mentioned earlier, many in public health believe that coinfection is so high because of "treatment optimism" -- the success of HAART leaving MSM feeling less at risk, leading to them taking more sexual risks. But Michael Rekart, M.D., and his colleagues, the authors of the current study, were skeptical as to whether such behavioral changes could be robust enough to account for such a large rise in syphilis. Their literature review found little to support the behavior change theory. Moreover, a purely behavioral explanation would not explain why the rise in syphilis rates among MSM are out of proportion to that of other STIs such as gonorrhea and chlamydia. Finally, they noted that the rise in syphilis also parallels the widespread availability of HAART.

Rekart and his colleagues suggested that these facts point to a biological rather than a behavioral explanation. They considered this hypothesis biologically plausible because, for the body to clear Treponema pallidum, it needs to call upon certain immune system functions, most notably a pro-inflammatory response. HAART can impair the immune system's ability to do this. Interestingly, the body does not rely on the same pro-inflammatory mechanisms to clear the bacteria that cause chlamydia or gonorrhea.

To test this hypothesis, the researchers created two mathematical models designed to predict syphilis rates. They used baseline data from the literature, and at the 20-year mark they introduced HAART and plotted predictions of syphilis rates under two scenarios. One model tried to make predictions based solely on an increase in risky behavior, and the other took the potential biological impact of HAART into account, as well. The behavior model actually predicted a lower rate of syphilis than real-life rates, but once they added the immune effects of HAART, the model closely approximated the true rate.

These results suggest that HIV-positive individuals on HAART, as well as HIV-negative individuals using the similar drugs as PrEP, are at higher risk of infection with the bacterium that causes syphilis. It is important to note, however, that this is still a theory and not a proven link between HAART and syphilis. More research is needed to confirm these results. Rekart suggests that they could be confirmed using laboratory studies with macaques followed by prospective cohort studies. Alternatively, the theory could be further examined using a retrospective case-control study comparing the prevalence of syphilis among patients who are taking HAART with those who are not. Additional studies should also look at whether certain drugs or drug combinations are more likely than others to have immunological effects.

Nonetheless, health care providers might want to explain the theory to their patients and begin to screen those on HAART for syphilis more often. Rekart and his colleagues are adamant, however, that their research should not be taken as a call for anyone to stop taking HAART. He told the Canada Journal "HAART drugs are life-saving; syphilis is curable."

Martha Kempner is a freelance writer, consultant and sexual health expert.


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Looking Back, Looking Forward: What's Next for STIs in MSM?
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Syphilis -- a Dreadful Disease on the Move
Basic Questions and Answers About Syphilis and Men Who Have Sex With Men (MSM)



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