Birth in the neonatal HBV vaccination era and hepatitis B surface antigen seroclearance in people with HIV and HBV coinfection on tenofovir-containing antiretroviral therapy.

Abstract

The impact of long-term tenofovir-containing antiretroviral therapy (ART) on hepatitis B surface antigen (HBsAg) seroclearance in people with HIV (PWH) and HBV coinfection remains under-defined, particularly in HBV-hyperendemic regions with universal vaccination programs. HBsAg-positive PWH receiving tenofovir-containing ART between 2011 and 2023 were followed until December, 2025. Demographics, HBV serologic markers, plasma HBV DNA, and liver fibrosis stage were collected. Cox proportional hazards models were used to identify factors associated with HBsAg seroclearance. Clinical and hepatic outcomes were compared by seroclearance status. After a median follow-up of 9.4 years, 35 (8.4%) of 415 PWH achieved HBsAg seroclearance during a total of 3,600 person-years of tenofovir-containing ART, corresponding to an incidence rate of 0.97 per 100 person-years. Among them, 37.1% (13/35) tested positive for anti-HBs at the time of seroclearance. In multivariable analysis, birth in universal neonatal HBV vaccination era (after July 1986) (adjusted hazard ratio [aHR] 13.56, 95% confidence interval [CI] 6.08-30.28, P<0.001), baseline HBsAg ≤250 IU/mL (aHR 7.36, 95% CI 3.29-16.50, P<0.001), and higher baseline ALT level (aHR 1.00 per 1-U/L increase, 95% CI 1.00-1.01, P<0.001) were independently associated with HBsAg seroclearance. None of PWH who achieved HBsAg seroclearance developed seroreversion, cirrhosis, or hepatocellular carcinoma, whereas 6.6% and 2.1% of PWH without seroclearance developed cirrhosis and hepatocellular carcinoma, respectively. Despite long-term tenofovir-containing ART, HBsAg seroclearance was uncommon (0.97% annually) among PWH with HBV coinfection. Birth in the neonatal HBV vaccination era and lower baseline HBsAg level were two independent predictors of HBsAg seroclearance.