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.
Highlights
In people living with the human immunodeficiency virus (HIV) worldwide, roughly 8.4%, or 3.2 million, are thought to be co-infected with chronic hepatitis B virus (HBV) infection [1]
Despite the optimal HBV DNA suppression offered by TDF-containing antiretroviral therapy (ART), HIV-HBV co-infected individuals do not appear to exhibit the same regression of liver fibrosis as observed in TDF-treated HBV mono-infected individuals [10,11,12] and a small proportion of co-infected individuals still exhibit hepatocellular carcinoma (HCC) [3]
hepatitis B surface antigen (HBsAg)-seroclearance rarely occurs in the majority of studies evaluating HIV-HBV coinfected individuals treated with potent anti-HBV containing ART
Summary
In people living with the human immunodeficiency virus (HIV) worldwide, roughly 8.4%, or 3.2 million, are thought to be co-infected with chronic hepatitis B virus (HBV) infection [1]. Despite the optimal HBV DNA suppression offered by TDF-containing ART, HIV-HBV co-infected individuals do not appear to exhibit the same regression of liver fibrosis as observed in TDF-treated HBV mono-infected individuals [10,11,12] and a small proportion of co-infected individuals still exhibit HCC [3]. These data contend that virological response might not be an adequate marker for improved prognosis and other criteria are needed to assess therapeutic success more adequately.
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