Clinical and Immunological Impact of Occult Hepatitis B Virus Infection Among HIV‐Infected Patients With and Without HCV Co‐Infection in Iran: A Cross‐Sectional Analysis

Occult hepatitis B infection (OBI), characterized by the presence of HBV DNA in HBsAg-negative individuals, poses a significant clinical risk among people living with HIV (PLWH), particularly in low-resource settings. This study aimed to assess the prevalence and clinical implications of OBI among HIV-positive patients with and without hepatitis C virus (HCV) co-infection in Hamadan Province, Iran. A cross-sectional study was conducted on 316 HIV-infected individuals receiving antiretroviral therapy (ART) from 2020 to 2023. Serological markers (HBsAg, anti-HBs, anti-HBc) were analyzed via ELISA. OBI was diagnosed using nested PCR, and viral loads were quantified by qPCR. Demographic, immunologic, and hepatic parameters were statistically compared between subgroups. The prevalence of OBI was 2.5% (8/316), with a higher occurrence among younger males and individuals with lower CD4+ counts. Co-infection with HCV was present in 21.5% of participants, among whom OBI rates were elevated. OBI-positive individuals exhibited altered liver enzyme levels and distinctive immunological profiles. Despite prior HBV vaccination in many cases, breakthrough OBI was observed, suggesting incomplete immune protection. OBI remains an underrecognized yet clinically significant comorbidity among PLWH. Regular HBV DNA screening, particularly in HCV-co-infected and immunocompromised individuals, is recommended to guide treatment decisions and mitigate liver-related complications.