A DECADE-long study has shed light on the risks of hepatitis D virus (HDV) superinfection in people with HIV (PWH) co-infected with hepatitis B virus (HBV), even in the era of tenofovir-containing antiretroviral therapy (ART). The research highlights the ongoing burden of HDV and its association with severe liver-related outcomes, despite the protective benefits of tenofovir.
Between 2011–2022, 534 HBV-coinfected PWH were followed, with anti-HDV antibody screening performed using archived blood samples. At baseline, 36 participants (6.7%) tested positive for HDV. Among 498 initially HDV-negative individuals, 50 (10.0%) seroconverted during the study period, equating to an HDV incidence rate of 12.54 per 1,000 person-years of follow-up. Notably, 88% of HDV seroconverters were men who have sex with men.
After a median follow-up of 10.2 years, during which tenofovir-containing ART covered 84.7% of the period, the study reported an all-cause mortality rate of 4.7%. HDV-infected participants faced disproportionately higher rates of liver-related complications, including liver-related mortality (3.5% versus 0.4%, P=0.032), cirrhosis (11.3% versus 3.6%, P=0.008), and hepatitis flares (28.2% versus 14.2%, P=0.001), compared to those without HDV. Multivariate Cox analysis revealed that HDV infection significantly increased the risk of liver-related death, with an adjusted hazard ratio of 9.696 (95% CI: 1.284–73.222, P=0.028). However, the incidence of hepatocellular carcinoma did not differ significantly between HDV-infected and HDV-uninfected individuals.
Despite advancements in HIV and HBV management with tenofovir-containing ART, HBV-coinfected PWH remain vulnerable to HDV superinfection and its severe liver-related outcomes. Clinicians are urged to maintain vigilance, regularly screening for HDV and monitoring for liver-related complications in this high-risk population.
Ada Enesco, EMJ
Reference
Huang YS et al. Incidence and outcome of hepatitis D virus infection in people with HIV in the era of tenofovir-containing antiretroviral therapy. Clin Infect Dis. 2025; DOI:10.1093/cid/ciae655.
