HBV core related antigen (HBcrAg) and HBV RNA are potential surrogate markers for intrahepatic HBV covalently closed-circular (ccc)DNA. cccDNA persists in infected hepatocytes despite HBV DNA suppression with antivirals. There are limited data on these markers in people with HIV-HBV co-infection on HBV-active antiviral therapy (ART).
People with HIV-HBV co-infection naïve to ART were recruited in Thailand in a prospective observational study. Liver fibrosis was measured by biopsy and transient elastography (TE) and blood and liver samples obtained pre- and following HBV-active ART. Liver HBV cccDNA was quantified using droplet digital PCR. HBcrAg and HBV RNA were measured in plasma using a chemiluminescence assay and high throughput test respectively. Differences between groups were assessed by Mann-Whitney and correlations by calculation of Spearman’s rank correlation coefficients.
Participants (n=37) were enrolled and followed for a median of 3.4 years of ART (n=18). They were mainly young men with median CD4+ T cell count pre- and on ART of 360 and 645 cells/µL respectively. At baseline, most had mild liver fibrosis (95% F0/F1 on biopsy) and the median (IQR) TE score was 6.2 (5.2, 8.1) kPa. At baseline and on ART, 61% and 28% were HBeAg positive respectively. cccDNA was quantified in 22 participants at baseline, 11 of them also had follow-up results. HBcrAg and HBV RNA were quantified in 30 at baseline, 17 also had follow-up results. cccDNA, HBcrAg and HBV RNA were lower in HBeAg negative versus positive individuals both pre- and on ART (p<0.005 for comparisons). Pairwise comparison of the same participants pre- and on ART showed no change in cccDNA (n=11) or HBV RNA (n=17) while HBcrAg decreased (n=17; p=0.034). Both HBcrAg and HBV RNA correlated with cccDNA pre-ART (n=22, HBcrAg r=0.67, p=0.001; HBV RNA r=0.76, p<0.0001). Pre-ART HBV RNA correlated with cccDNA in eAg positive participants (n=16, r=0.54, p=0.041). In eAg negative participants cccDNA was negative in 5/6 (3 also had negative HBV RNA). On ART both HBcrAg and HBV RNA correlated with cccDNA (n=17; HBcrAg r=0.81, p<0.0001; HBV RNA r=0.77, p=0.0002) and in the HBeAg negative subset (n=12; HBcrAg r=0.58, p=0.042; HBV RNA r=0.59,p=0.046).
Following HBV-active ART in people living with HIV-HBV co-infection, there is no change in cccDNA or HBV RNA. On ART both HBV RNA and HBcrAg correlate with cccDNA including amongst HBeAg negative participants, consistent with findings in HBV monoinfection.