Disclosures: Marcus Dorner – Grant/Research Support: CN Bio Innovations, Ltd The following people have nothing to disclose: Eva Billerbeck, Michiel C. Mom-mersteeg, Amir Shlomai, Jing W. Xiao, Linda Andrus, Ankit

Bhatta, Anuradha Krishnan, Michael Charlton, Luis Chiriboga, Charles M. Rice, Ype P. De Jong Covalently closed circular DNA (ccc-DNA) of hepatitis B virus (HBV) acts as a reservoir for reactivation of viral replication and whose quantification can be used as a marker of persistent intracellular replication. The determinants of intracellular levels of replication have rarely been evaluated in HBV-human immunodeficiency virus (HIV) co-infected patients. Sixty HIV-HBV co-infected patients PCI-32765 chemical structure with at least one liver biopsy during follow-up in the French HIV-HBV cohort were included. HBV ccc-DNA and total intracellular HBV-DNA were extracted from biopsies and quantified by real-time PCR. Risk-factors of intra-cellular replication were determined using mixed-effect linear regression models. At the time of biopsy, 35 (61.4%) patients were HBeAg-positive and 23 (46.9%) had detectable serum HBV-DNA (median: 3.10 log10 IU/mL, IQR:2.75-5.38). Among the 22 patients undergoing tenofovir (TDF)-containing antiretroviral therapy, cumulative

TDF-duration was at a median 17.8 months (IQR:5.7-31.0). Overall, median HBV ccc-DNA was -1.10 log10 copies/cell (IQR:-1.70, check details -0.29) and total intra-cellular HBV-DNA was 0.27 log10 copies/cell (IQR:-0.39, 2.00). In multivariable analysis, patients with HBeAg-posi-tive serology had significantly higher levels of HBV ccc-DNA

(+0.76 log10 copies/mL; 95%CI:0.39, 1.13; p<0.001), whereas those with a nadir CD4+ cell count above 250/mm3 had significantly lower HBV ccc-DNA levels (-0.57 log10 learn more copies/mL; 95%CI:-0.95, -0.19; p=0.004). Furthermore, patients with longer than 3 years of cumulative TDF-duration had significantly lower HBV ccc-DNA levels after adjustment (-0.88 log10 copies/cell: 95%CI:-1.40, -0.35; p=0.001). Accordingly, when focusing on patients undergoing TDF with a biopsy at TDF-initiation and sometime during therapy (median duration: 35.3 months, range: 20.2-56.6), most exhibited strong declines in HBV ccc-DNA (median change in log10 copies/ cell/year:-0.46, range:-0.67, 0; n=7). HBV ccc-DNA levels did remain detectable at the end of follow-up for all patients, yet at very low levels (median: 0.04 copies/cell, range: 0.01, 0.31). The results above were similar when using total intracellular HBV-DNA levels as an end-point. In conclusion, severe immu-nosuppression is associated with intracellular HBV replication in coinfected patients. Treatment with TDF is linked to large declines in ccc-DNA, yet replication within the hepatocyte still persists after long periods of treatment.