A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?

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dc.contributor.authorRekart, Michael L.
dc.contributor.authorNdifon, Wilfred
dc.contributor.authorBrunham, Robert C.
dc.contributor.authorDushoff, Jonathan
dc.contributor.authorPark, Sang Woo
dc.contributor.authorRawat, Sanjana
dc.contributor.authorCameron, Caroline E.
dc.date.accessioned2018-10-10T12:43:02Z
dc.date.available2018-10-10T12:43:02Z
dc.date.copyright2017en_US
dc.date.issued2017
dc.description.abstractBackground and hypothesis: 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 (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic. Methods: We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects. Conclusions and implications: Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. 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. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such as T. pallidum.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01AI015334 and R01AI123196 (CEC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.en_US
dc.identifier.citationRekart, M.L.; Ndifon, W.; Brunham, R.C.; Dushoff, J.; Park, S.W.; Rawat, S.; & Cameron, C.E. (2017). A double-edged sword: Does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?. Sexually Transmitted Infections, 93(5), 374-378. http://dx.doi.org/10.1136/sextrans-2016-052870en_US
dc.identifier.urihttp://dx.doi.org/10.1136/sextrans-2016-052870
dc.identifier.urihttp://hdl.handle.net/1828/10150
dc.language.isoenen_US
dc.publisherSexually Transmitted Infectionsen_US
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleA double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?en_US
dc.typeArticleen_US

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