BACKGROUND AND AIMS: Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing ART in a large multi-cohort study. METHODS: We included all HIV-infected adults with a positive hepatitis B surface antigen followed in one of four prospective European cohorts. The primary outcome was the occurrence of HCC. Demographic and clinical information was retrieved from routinely collected data, and liver cirrhosis was defined according to results from liver biopsy or non-invasive measurements. Multivariable Poisson regression was used to assess HCC risk factors. RESULTS: 3,625 HIV/HBV-coinfected patients, of whom 72% have initiated TDF-containing ART were included. Over 32,673 patient-years (py), 60 individuals (1.7%) developed an HCC. The incidence of HCC remained stable over time among individuals on TDF, whereas it increased steadily among those not on TDF. Among individuals on TDF, the incidence of HCC was 5.9 per 1,000 py (95% confidence interval [CI] 3.60-9.10) in cirrhotics and 1.17 per 1,000 py (0.56-2.14) among non-cirrhotics. Age at initiation of TDF (adjusted incidence rate ratio per 10 years increase: 2.2, 95% CI 1.6-3.0) and the presence of liver cirrhosis (4.5, 2.3-8.9) were predictors of HCC. Among non-cirrhotic individuals, the incidence of HCC was above the commonly used screening threshold of 2 cases per 1,000 py only in patients aged >46 years at TDF initiation. CONCLUSIONS: Whereas the incidence of HCC was high in cirrhotic HIV/HBV-coinfected individuals, it remained below the HCC screening threshold in patients initiating TDF without cirrhosis at an age <46 years. Lay summary: We investigated the incidence of hepatocellular carcinoma (HCC) in HIV/HBV-coinfected individuals from a large multi-cohort study in Europe. Over 32,673 patient-years, 60 individuals (1.7%) developed an HCC. The incidence of HCC remained low in patients initiating TDF without cirrhosis at an age <46 years.Read less <