title: A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity toTreponema pallidum?
abstract: 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 toTreponema pallidumand that this biological explanation plays an important role in the syphilis epidemic.
  
  
  
  We performed a literature search and developed a mathematical model of HIV-1 andT. pallidumconfection 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.
  
  
  
  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 toT. 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 enhancedT. pallidumsusceptibility are needed. If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such asT. pallidum.
authors.affiliation: School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rekart
authors.affiliation: African Institute for Mathematical Sciences, Muizenberg, Cape Town, South Africa.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Ndifon
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dushoff
authors.affiliation: Department of Mathematics and Statistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Sanjana
authors.initials: S
authors.lastname: Rawat
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Cameron
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D006069:Gonorrhea; D015658:HIV Infections / Q000453:epidemiology / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D015497:HIV-1 / Q000276:immunology; D018451:Homosexuality, Male; D006801:Humans; D015994:Incidence; D008297:Male; D008962:Models, Theoretical; D015995:Prevalence; D012309:Risk-Taking; D012749:Sexually Transmitted Diseases / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology / Q000635:transmission; D013587:Syphilis / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology*; D014210:Treponema pallidum / Q000187:drug effects / Q000276:immunology*
keywords: ANTERETROVIRAL THERAPY; HIV; INFECTION; MATHEMATICAL MODEL; SYPHILIS