Drug-resistant and immune-escape hepatitis B virus mutants in HIV-infected hosts

HIV-HBV infected patients require optimal control of viral replication in order to prevent severe comorbidities, such as liver cirrhosis and hepatocellular carcinoma. The genetic diversity of HBV is a poorly investigated factor of such viral replication in HIV-infected hosts. HBV genome diversity can be differentiated in two major aspects: genotypic and phenotypic. Genotypic diversity is more related to the natural history of HBV infection and genotypes are mostly determined by geographical origin. Phenotypic diversity arises from attempts to escape from host immune surveillance (i.e. Precore, Core, and Basal Core Promoter mutants), selection due to the use of treatments with weak genetic barrier (i.e. Pol mutants), exposure to hepatitis B immunoglobulin (i.e. " immune-escape " S mutants), or treatment-induced mutations from overlapping genes (i.e. Pol mutants inducing " vaccine-escape " S mutants). Pol mutations typically lead to uncontrolled viral replication, whereas S gene mutations can significantly alter HBsAg synthesis and reduce binding to antiHBs antibodies, which renders persons vaccinated or cured of HBV-infection susceptible to infection. During coinfection with HIV, treatment options must be seriously considered with the aim of reducing the risk of HBV mutations, thereby preventing their clinical consequences for which the public health implications are fairly unknown.