Consequences of persistent HBV infection in HIV: the double-edged sword of nucleos(t)ide analogs

Abstract

A variety of nucleos(t)ide analogs (NA) are available to treat HBV infection, the majority of which are also active against HIV, and when alone or in combination, have proven to actively suppress circulating HBV. However during treatment, especially among HIV-infected patients, the persistent nature of replicating intracellular DNA and lack of HBsAg loss indicates the potential for NA resistance and hence changes in HBV genetic variability. Meanwhile, cytotoxic CD8+ T cells responsible for clearing infected hepatocytes appear to become exhausted and anti-HBV immunoglobulin-producing B cells become deficient; both of which can be altered during HIV infection. Furthermore, host-determinants, specifically regulation of HBV integration into the host genome and polymorphisms on the HLA allele, have been shown to affect HBV replication. Studies on how these selective pressures influence HBV genetic variability are sparse, yet lead to important considerations on NA resistance during persistent infection.