title: Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals.
abstract: After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2-1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation.
authors.affiliation: aDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich bInstitute of Medical Virology, University of Zurich, Zurich cBasel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel dInfectious Diseases Department, Genève University Hospital, Genève eInfectious Diseases Department, Lausanne University Hospital, Lausanne fDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel gDivision of Infectious Diseases and Hospital Epidemiology, Kantonal Hospital St. Gallen, St. Gallen hDivision of Infectious Diseases, Regional Hospital Lugano, Lugano iDepartment of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Mohaned
authors.initials: M
authors.lastname: Shilaih
authors.forename: Alex
authors.initials: A
authors.lastname: Marzel
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Braun
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.forename: Helen
authors.initials: H
authors.lastname: Kovari
authors.forename: Jim
authors.initials: J
authors.lastname: Young
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Katharine
authors.initials: K
authors.lastname: Darling
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Thurnheer
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kouyos
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015897:Comorbidity; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology*; D020010:Heterosexuality / Q000706:statistics & numerical data; D018451:Homosexuality, Male / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use; D012307:Risk Factors; D015819:Substance Abuse, Intravenous / Q000453:epidemiology; D013587:Syphilis / Q000453:epidemiology*; D047568:Unsafe Sex
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine