ed patients, HIV-infected patients. Values on bars are number of subjects testing positive/total number tested. Error bars show 95% confidential intervals. doi:10.1371/journal.pone.0133589.g002 5 / 13 CE Trends and Risks 6 / 13 CE Trends and Risks CE, candida esophagitis; HIV, human immunodeficiency virus; IQR, interquartile range; HAART, highly active anti-retroviral therapy; HBV, hepatitis B virus; HCV, hepatitis C virus; NSAIDs, non-steroidal anti-inflammatory drugs; H2RA, H2-receptor antagonist. Data are presented as number or mean SD. p values for the comparison between patients with CE and those without CE. doi:10.1371/journal.pone.0133589.t001 The risk factors identified by multivariate analysis for HIV-infected and non-HIV-infected patients are shown in Discussion In this study, we identified that, over the 13-year period from 2002 to 2014, CE prevalence showed significant increases in non-HIV-infected patients but decreases in HIV-infected patients. Moreover, risk analysis revealed that increasing age, HIV infection, and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19747723 corticosteroids use were independently associated with CE, but alcohol, other infections, diabetes, anticancer drugs, and antisecretory drug use were not. Among HIV-infected patients, low CD4 cell count and absence of HAART were independent risk factors for CE. In corticosteroid users, higher prednisone-equivalent daily corticosteroid dose significantly increased CE risk. CE prevalence in non-HIV-infected patients is reported to 0.37.3%, which is consistent with our findings of 1.5% in non-HIV-infected patients. Similarly for HIV-infected 7 / 13 CE Trends and Risks OR, odds ratio; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; NSAIDs, non-steroidal anti-inflammatory drugs; H2RA, H2-receptor antagonists; NA, not applicable. Values in parentheses represent 95% confidential intervals. doi:10.1371/journal.pone.0133589.t003 patients, CE prevalence was reported to be 42.851.8% in the pre-HAART era and 8.5 16.7% in the HAART era, with which our finding of 9.8% prevalence in HIV-infected patients, most of whom received HAART, concurs. Little information about CE trends has been available to date, and most order Aphrodine studies have focused on HIV-infected patients. Declining CE incidence has been reported in this patient population by Mocroft et al, from 5.7 person-years in 1994 to 0.5 person-years in 2004, and Nkuize et al, from 42.8% in 19911994, 23.5% in 19992002, and 16.7% in 20052008. Likewise, CE prevalence decreased from 13.6% in 20022003 to 9.0% in 20122014 in the present study. This is probably due to the introduction of HAART, which PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19748727 helped avoid immunodeficiency, and the development of effective prophylaxis against opportunistic infection. In contrast, CE prevalence in non-HIV-infected patients showed a significant increase over the same 
period, likely because, in a rapidly aging society, more people have comorbidities and take immunosuppressants, which can lead to the development of CE. Several risk factors for CE have been investigated in case-control studies, although these studies had a small number of CE cases and retrospective in nature. They identified corticosteroid or PPIs use, heavy drinking, uncontrolled DM, and cancer as CE risk factors. In our larger scale study investigating the very same factors, multivariate analysis similarly identified systemic corticosteroid use but also revealed increasing age and HIV infection as risk factors for CE. 8 / 13 CE Trends and Risks Non-HI