Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

Abstract

In individuals infected with hepatitis B virus (HBV), the loss of hepatitis B surface antigen (HBsAg) is the ultimate therapeutic goal, which defines “functional cure.” For individuals living with human immunodeficiency virus (HIV), functional cure occurs roughly 2 per 100 person-years during potent anti-HBV containing antiretroviral therapy. Although this rate may be higher than expected in treated HBV mono-infected individuals, rates of functional cure widely vary between studies (0.6–10.5 per 100 person-years). Similar to HBV mono-infection, the phase of HBV infection, HBV (sub-)genotypes and hepatitis B “e” Ag-negative variants are associated with functional cure in treated HIV-HBV co-infection. In specifically HIV-HBV co-infected individuals, strong increases in CD4+ T cell counts after treatment initiation have also been linked to functional cure, yet this finding is inconsistent across studies. Several markers directly or indirectly reflecting HBV activity are being developed to predict functional cure, such as quantification of HBsAg, hepatitis B core-related antigen, HBsAg protein composition, anti-hepatitis B core antibodies and interferon-gamma-inducible protein 10. Few have been assessed during treatment in HIV-HBV co-infected individuals and none have been validated to predict functional cure. Novel therapeutics for HBV cure are essential for individuals with HIV-HBV co-infection and need to be separately evaluated in this population.

Incidence and predictors of HBV functional cure in patients with HIV/HBV coinfection: A retrospective cohort study

“…Previously, we conducted a meta-analysis that showed that the rate of HBsAg clearance in patients with HIV/HBV coinfection treated with TDF-containing regimens was approximately 7.3% ( Jiang et al., 2019 ), which is similar to the finding reported by Boyd et al. ( Boyd et al., 2021 ). Recently, several studies in Caucasians and Thailand found that ethnicity, HBV viral load, CD4 cell count, HBeAg, and quantification of HBsAg were significantly associated with HBsAg clearance among patients with HIV/HBV coinfection treated with long-term TDF-containing ART ( Zoutendijk et al., 2012 ; Matthews et al., 2013 ; Jiang et al., 2019 ; Audsley et al., 2020 ; Bremen et al., 2020 ).…”

High rates of hepatitis B virus (HBV) functional cure among HIV/HBV coinfected Chinese adults on antiretroviral therapy

“…HBsAg clearance/loss with or without development of hepatitis B surface antibody (anti-HBs) is regarded as a “functional cure” for HBV mono-infection [8] . Functional cure decreases the risk of liver disease progression and development of HCC [8,9] . In short, this is the ultimate treatment target for HIV/HBV coinfected individuals.…”

“…[ 8 ] Functional cure decreases the risk of liver disease progression and development of HCC. [ 8 , 9 ] In short, this is the ultimate treatment target for HIV/HBV coinfected individuals.…”

Hepatitis B surface antigen loss in individuals with chronic hepatitis B virus and HIV-1 infections in Botswana

“…Thus treatment aims to improve clinical outcome and life expectancy [12]. The use of HBsAg seroclearance as the definition of functional HBV cure is founded on the idea that it is usually associated with decreased risk of HCC, longevity, and long-term suppression of the HBV replication [13,14]. Other HBV serological markers also have different clinical significance.…”