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.

Figure 1

The number of unique Swiss HIV Cohort study patients tested per year and the number of syphilis tests they underwent are shown for the years 2005 to 2014. The number of syphilis cases is shown in 1000 patient-years per transmission group. The vertical axis is log-scaled and dots below 1 represent years with 0 syphilis cases. HET = heterosexual, IDU = intravenous drug use, MSM = men who have sex with men.

Figure 2

Teal-colored dots and confidence intervals (CIs) represent the incidence rate of syphilis in the Swiss HIV Cohort study between 2005 and 2014, cases per 1000 person-years (for easier trend visualization, the blue line is a natural cubic spline fitted to the incidence rate, the gray shaded region shows the estimated 95% CI). The red dots show the absolute number of incident cases per year (the red line represents a natural cubic spline fitted to the absolute number of cases).