Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co-infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well-established) differs between HBV-HIV co-infection vs. HBV mono-infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV-HIV Ancillary Study and 105 participants in the HBRN mono-infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p <.05) in the HBV-HIV versus the HBV-only sample (HBeAg: 1.05 vs. 0.51 log₁₀ IU/mL; HBsAg: 3.85 vs. 3.17 log₁₀ IU/mL; HBV RNA: 5.60 vs. 3.70 log₁₀ U/mL; HBcrAg: 6.59 vs. 5.51 log₁₀ U/mL). Conversely, among HBeAg(−) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log₁₀ U/mL) were lower (p <.05) in HBV-HIV vs. HBV-only; HBcrAg levels were similar (4.14 vs. 3.64 log₁₀ U/mL; p =.27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co-infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status.