Incidence and Outcome of Hepatitis D Virus Infection in People With HIV and Hepatitis B Virus Coinfection in the Era of Tenofovir-Containing Antiretroviral Therapy.

Abstract

Tenofovir-containing antiretroviral therapy (ART) improves survival in hepatitis B virus (HBV)-coinfected people with HIV (PWH). We investigated the incidence of hepatitis D virus (HDV) infection and its clinical impact in HBV-coinfected PWH in the era of tenofovir-containing ART. 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. Timing of incident HDV infection was estimated as the midpoint between the last timepoint of anti-HDV-negative samples and the first timepoint of anti-HDV-positive samples. Differences in survival and liver-related outcomes between HDV-infected and -uninfected PWH were analyzed. 534 HBV-coinfected PWH were included; 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), all-cause mortality was 4.7% (25/534). PWH with HDV 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). Risk of hepatocellular carcinoma was similar for HDV-infected and HDV-uninfected PWH. HBV-coinfected PWH remain at risk of HDV superinfection and HDV infection is associated with liver-related death in the era of tenofovir-containing ART.