Kinetics of hepatitis B virus replication in anti-HBc positive/HBsAg-negative people with HIV switching to tenofovir sparing therapy

Objectives: To unravel the still unexplored HBV-replicative kinetics in anti-HBc-positive/HBsAg-negative people-with-HIV (PWH) suspending tenofovir disoproxil-fumarate/tenofovir-alafenamide (TDF/TAF). Methods: A total of 101 anti-HBc-positive/HBsAg-negative PWH switching to TDF/TAF-sparing therapy were included. Serum HBV-DNA and HBV-RNA were quantified by droplet-digital-PCR at switching (T0), within 12 months (T1) and 12-24 months postswitch (T2). Results: At T0, 33.7% had cryptic HBV-DNA (undetected by commercial assays, median [interquartile range (IQR)]: 2 [1-5] IU/mL) and 22% were positive to HBV-RNA alone (median [IQR]: 4 [3-4] IU/mL), indicating an active HBV-reservoir despite HBsAg-negativity and TDF/TAF-pressure. Notably, anti-HBs-titer <100 mIU/mL independently correlated with cryptic HBV-DNA at T0 (OR [95% CI]: 2.6 [1.02-6.5], P = 0.04). After TDF/TAF-withdrawal, the rate of PWH achieving HBV-DNA >10 IU/mL increased from 12.9% at T1 to 42.6% at T2 (P < 0.0001). Likewise, a rise from 2 to 11% was observed for HBV-DNA >100 IU/mL (P = 0.02); median (IQR) HBV-DNA: 579 (425-770) IU/mL. Notably, HBV-DNA >10 IU/mL at T2 occurred in 70% of PWH with cryptic HBV-DNA, in 38.5% with HBV-RNA alone and in 25% negative to both HBV-markers at T0 (P = 0.01). Cryptic HBV-DNA at T0 and lower nadir CD4+ T-cell-count independently predicted HBV-DNA >10 IU/mL at T2 (OR [95% CI]: 8.2 [1.7-40.6], P = 0.01; OR [95% CI]: 8.1 [1.3-52.1], P = 0.03). Lastly, persistent HBV-DNA positivity was independently associated with a reduced CD4+ T-cell recovery at T2 (OR [95% CI]: 0.07 [0.01-0.77], P = 0.03). Conclusion: This study underlines the importance to regularly monitor anti-HBc-positive/HBsAg-negative PWH undergoing TDF/TAF-sparing regimen and the role of highly-sensitive HBV markers in optimizing their management.