Background:  Hepatitis delta virus (HDV) is a human virus that is associated with co-infection and super-infection of hepatitis B virus (HBV) carriers. HDV has a unique replication process and uses the host cellular polymerase. The hepatitis B surface antigen (HBsAg) is essential in the HDV lifecycle and its quantification could be useful in the management of chronic HDV patients. Recent reports have highlighted that long-term, suppressive anti-HBV therapy may reduce HDV viremia and lessen liver damage. Although this is likely due to a reduction in HBsAg expression needed for HDV particle assembly, this hypothesis has not yet been demonstrated.

Methods:  A longitudinal study was carried out in all HIV patients attended our hospital who had chronic HDV following HAART containing lamivudine, tenofovir, or emtricitabine. HBV and HIV serological assays were analyzed by enzyme immunoassay (EIA) using AxSym systems and HDV serology by Radim EIA. Serum HDV RNA was quantified as described by le Gal et al., and serum HBV DNA was quantified using Roche Cobas TaqMan. HBsAg was quantified by enzyme-linked immunosorbent assay (ELISA) using Monolisa HBsAg Ultra and a National Institute for Biological Standards and Control (NIBSC) standard.

Results:  A total of 16 HIV patients with chronic HDV were included in the study. A significant correlation was found between serum HDV RNA and HBsAg levels (r = 0.557, p <0.0001), but not between HBV DNA and HBsAg (r = –0.083, p <0.392). Moreover, 10 patients showed a simultaneous decrease in both serum HDV RNA and HBsAg levels following initiation of therapy. Baseline HDV RNA and HBsAg were 7.7 log copies/mL and 15750 IU/mL, respectively, and after a median of 6.1 years of HAART-containing active anti-HBV drugs dropped to 5.6 log copies/mL and 2878 IU/mL, respectively. For the remaining 6 patients, there was no significant change in serum HBsAg and HDV RNA levels despite successful anti-HBV treatment, as shown by undetectable serum HBV DNA.

Conclusions:  There is a good correlation between serum HDV RNA and HBsAg levels in most HIV-infected patients with chronic HDV receiving HAART-containing active anti-HBV drugs. This is one of the first indications of indirect activity of anti-HBV nucleos(t)ide analogs against HDV. Quantification of HBsAg could be a useful surrogate tool for monitoring HDV replication in patients undergoing anti-HBV therapy. The lack of correlation between serum HBV DNA and HBsAg levels may be due to high levels of circulating HDV particles trapping HBsAg.