Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (ARV) for HIV-1 infection.

Treatment with ARV reduces risk of infection (because of greatly reduced viral load) and near-normal life expectancy for those on treatment. The currently accepted hypothesis is that these factors result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 sexually transmitted infections, including gonorrhoea, chlamydia and syphilis.

However, syphilis incidence has increased more rapidly than other STDs. In a recent open access article in the journal Sexually Transmitted Infections, Reckart and colleagues hypothesise that ART itself  may alter the innate and acquired immune responses to Treponema pallidum, the bacterium causing infectious syphilis, and that this biological explanation plays an important role in the current syphilis epidemic.

In a leading article in the same journal, Susan Tuddenham and colleagues (only available to subscribers), find the hypothesis intriguing despite some flaws. They go on to suggest that further work is necessary to look at the mechanisms underlying the current syphilis epidemic.

In the same issue David Glidden et al point out that in the early double blind trials with pre-exposure prophylaxis (PrEP) no increase in syphilis was found between those taking PrEP and those taking placebo. These findings would suggest that short term exposure to ART has no effect on the acquired immune responses to Treponema pallidum.