title: Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial.
abstract: BACKGROUND
  Syphilis infection may potentiate transmission of human immunodeficiency virus (HIV). We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV preexposure prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified that association.
  
  
  METHODS
  The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed.
  
  
  RESULTS
  Of 2499 individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the trial was 7.3 cases per 100 person-years. There was no difference in syphilis incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs 6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6 (95% confidence interval, 1.6-4.4; P < .001). There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence.
  
  
  CONCLUSIONS
  In HIV-seronegative MSM, syphilis infection was associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated.
authors.affiliation: The Gladstone Institutes University of California, San Francisco.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Solomon
authors.affiliation: Fenway Health, Beth Israel Deaconess Medical Center, Fenway Institute Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.affiliation: University of California, San Francisco.
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.affiliation: Bridge HIV, San Francisco Department of Public Health, California.
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Liu
authors.affiliation: The Gladstone Institutes.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: McMahan
authors.affiliation: Investigaciones Medicas en Salud, Lima, Peru.
authors.forename: Juan V
authors.initials: JV
authors.lastname: Guanira
authors.affiliation: Research Institute for Health Sciences and Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Thailand.
authors.forename: Suwat
authors.initials: S
authors.lastname: Chariyalertsak
authors.affiliation: Fundacion Ecuatoriana Equidad, Guayaquil, Ecuador.
authors.forename: Telmo
authors.initials: T
authors.lastname: Fernandez
authors.affiliation: The Gladstone Institutes University of California, San Francisco.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000635:transmission*; D018451:Homosexuality, Male; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage; D010919:Placebos / Q000008:administration & dosage; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D015995:Prevalence; D013587:Syphilis / Q000150:complications* / Q000453:epidemiology / Q000635:transmission*; D000068698:Tenofovir; D063106:Transgender Persons; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D010919:Placebos; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
keywords: HIV prevention; MSM; chemoprophylaxis; preexposure prophylaxis; syphilis