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Antiretrovirals might raise susceptibility to syphilis

If confirmed, this makes STI screening in gay and bisexual men an even greater priority

Louise Prime

Tuesday, 17 January 2017

Antiretroviral drugs used to treat human immunodeficiency virus (HIV) might make men who have sex with men (MSM) more susceptible to becoming infected with syphilis, researchers have concluded in their review,* published today in Sexually Transmitted Infections. The authors of an accompanying editorial** expressed reservations about the study, but said if further research backs up this “intriguing” hypothesis, this will provide one more reason to prioritise screening, diagnosis and treatment of sexually transmitted infections (STIs) in MSM.

The research team, led from the University of British Columbia in Vancouver, Canada, explained that the prevailing hypothesis to explain the rapidly escalating rate of syphilis (Treponema pallidum) infection in MSM globally is that the availability of highly active antiretroviral therapy (HAART) increases risky sexual behaviour, because both HIV-infected and non-infected people perceive that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. But this does not explain why rates of syphilis among MSM should be so much higher than those of chlamydia or gonorrhoea.

The researchers investigated an alternative hypothesis, that HAART downregulates the innate and acquired immune responses to Treponema pallidum, and that this plays an important role in the syphilis epidemic. To explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects, they conducted a literature search and developed a mathematical model of HIV-1 and T. pallidum co-infection in a population with two risk groups, with assortative mixing between groups.

Their calculations showed that either behavioural or biological factors could produce outbreaks of syphilis that would be substantially higher than expected – but that the combination of both factors produced a peak in the number of infections that was greater than that associated with either factor alone, and produced similar figures to those in the current outbreak. They said that behavioural change alone is not enough to explain the “the unique, sharp increase in syphilis incidence” which “appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM”.

They concluded: “HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. 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.”

In their accompanying editorial, infectious disease experts argued that the rise in syphilis cases might simply reflect inadequate screening for chlamydia and gonorrhoea, and pointed out that previous outbreaks of syphilis in straight men and women occurred before the advent of HAART. They also argued that the researchers’ models failed to take account of the complexities of sexual relationships.

However, they said the hypothesis is “intriguing” and “warrants careful consideration”. They concluded: “If further investigations support a role for antiretroviral therapy in increasing susceptibility to syphilis, this will provide one more reason why screening, diagnosis and treatment of STIs in MSM must be prioritised.”



* Rekart ML, Ndifon W, Brunham RC, et al. A double edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum? Sex Transm Infect 2017. DOI: 10.1136/setrans-2016-052870

** Tuddenham S, Shah M, Ghanem KG. Syphilis and HIV: is HAART at the heart of this epidemic? Sex Transm Infect 2017. DOI: 10.1136/sextrans-2016-052940

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