Incidence and outcome of hepatitis D virus infection in people with HIV in the era of tenofovir-containing antiretroviral therapy

Background Tenofovir-containing antiretroviral therapy (ART) improves survival in HBV-coinfected people with HIV (PWH). We investigated the incidence of HDV infection and its clinical impact in HBV-coinfected PWH in the era of tenofovir-containing ART. Methods Between 2011 and 2022, HBV-coinfected PWH were included and followed until December 2023. Anti-HDV antibody screening was performed using sequentially archived blood samples. The timing of incident HDV infection was estimated as the midpoint between the last time point of anti-HDV-negative samples and the first time point of anti-HDV-positive samples. Differences in survival and liver-related outcomes between HDV-infected and HDV-uninfected PWH were analyzed. Results 534 HBV-coinfected PWH were included and 36 (6.7%) tested HDV-seropositive at baseline. During 3987.78 person-years of follow-up (PYFU), 50 (10.0%) of 498 anti-HDV-negative PWH seroconverted for HDV, with an overall incidence rate of 12.54 per 1000 PYFU. 88.0% (44/50) of HDV seroconverters were men who have sex with men. After a median follow-up of 10.2 years (84.7% of the follow-up period covered by tenofovir-containing ART), the all-cause mortality was 4.7% (25/534). HDV-infected PWH had significantly higher rates of liver-related mortality (3.5% vs 0.4%, P=.032), cirrhosis (11.3% vs 3.6%, P=.008), and hepatitis flare (28.2% vs 14.2%, P=.001) than HDV-uninfected PWH. In multivariate Cox analysis, HDV infection was associated with liver-related mortality (adjusted HR, 9.696; 95% CI, 1.284-73.222, P=.028). The risk of hepatocellular carcinoma was similar for HDV-infected and HDV-uninfected PWH. Conclusions HBV-coinfected PWH remain at risk for HDV superinfection and HDV infection is associated with liver-related death in the era of tenofovir-containing ART.