Risk of Inflammatory Bowel Disease in HIV Patients: A Danish Cohort Study (1983-2018) with American Validation (1999-2018)

Background: HIV infection is implicated in the development of several immune mediated disorders, but the risk of inflammatory bowel disease (IBD) in people living with HIV (PLWH) remains uncertain. We aimed to study the risk of IBD among PLWH in a nationwide population-based Danish cohort study and to validate our findings with a US insurance-based database. Methods: Using Danish national patient registers (1983-2018), we identified a cohort of 8,995 PLWH who were matched to 449,750 HIV-negative individuals by age and sex, and followed for 7,154,999 person-years. Cumulative incidence of IBD in PLWH compared with matched non-HIV individuals was calculated. Cox regression analysis was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for development of IBD. Findings were validated using a US insurance-based cohort, Explorys (1999-2018), with results reported as odds ratios (OR) with 95% CI. Findings: The risk of IBD was significantly increased among PLWH in Denmark (HR: 2.24, 95% CI: 1.78-2.82) compared with the matched non-HIV population. This was seen for both Crohn’s disease (HR: 2.18, 95% CI: 1.43-3.34) and ulcerative colitis (HR: 2.22, 95% CI: 1.68-2.92) and in both the pre- and post-HAART era (pre-1996 HR: 2.30, 95% CI: 1.55-3.42; 1996-onwards HR: 2.11, 95% CI: 1.59-2.80). Risk was also increased in male (HR: 2.75, 95% CI: 2.15-3.52) but not female Danish PLWH (HR: 0.93, 95% CI: 0.48-1.79). US cohort analysis confirmed an increased risk of IBD in PLWH compared with non-HIV individuals (OR: 1.41, 95% CI: 1.35-1.49). Interpretation: This study finds a significantly increased risk of IBD among PLWH in both a Danish and US population. Further research into the interplay between HIV, IBD, and the impact of antiretroviral therapy on this relationship is required. Funding Statement: PSD is supported by the American Gastroenterology Association Research Scholar Award alongside Digestive Diseases Research Center grant and National Institue of Health grant (DK120515). Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: TJ currently holds approval from the Danish Data Protection Agency for projects with datasets extracted from Danish national registers. Use of Explorys data does not require ethical review board approval. Ethical approval is not required for register-based research in Denmark.