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 antiHBc-positive/HBsAg-negative people-with-HIV (PWH) suspending TDF/TAF.

Methods: 101 antiHBc-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 post-switch (T2).

Results: At T0, 33.7% had cryptic HBV-DNA (undetected by commercial assays, median[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, antiHBs-titer<100mIU/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>10IU/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>100IU/ml (P=0.02); median(IQR) HBV-DNA: 579(425-770)IU/ml. Notably, HBV-DNA>10IU/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>10IU/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).

Conclusions: This study underlines the importance to regularly monitor antiHBc-positive/HBsAg-negative PWH undergoing TDF/TAF-sparing regimen and the role of highly-sensitive HBV markers in optimizing their management.