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Antiviral effect of therapy with REP 2139-Ca and nucleos(t)ide analogues against HBV in vivo
Treatment of human patients with chronic HBV infection with the nucleic acid polymer (NAP) REP 2139 results in the elimination of circulating HBsAg. In this preclinical study we evaluated a novel combination therapy associating REP 2139-Ca with tenofovir diso- proxil fumarate (TDF) and entecavir (ETV), in vivo, in the DHBV infection model.
DHBV-carrier ducks were treated for 4 weeks with normal saline (IP), REP 2139-Ca (10 mg/kg IP QD), TDF (15 mg PO QD), REP 2139-Ca + TDF or REP 2139-Ca + TDF + ETV (1 mg PO QD). Serum DHBsAg was monitored by ELISA and DHBV DNA by qPCR. After therapy cessation all animals were followed during additional 8 weeks. Total DHBV DNA and cccDNA were analyzed in autopsy liver samples by qPCR.
On-treatment antiviral responses were more marked when REP 2139 was combined with TDF or TDF and ETV. Sustained virologic responses (SVR) during 2 months off-therapy were only observed in the groups receiving REP 2139 alone or in combination with TDF or TDF and ETV but not in TDF-monotherapy. SVR consisted of stably suppressed serum DHBsAg and DHBV DNA and significant decrease in liver DHBV DNA and cccDNA that were more marked in com- bination-therapy groups. Importantly, SVR animals had undetectable liver DHBsAg as assessed by immunostaining analysis.
Antiviral performance of REP 2139 was sustained and enhanced by combination with TDF or ETV. Thus an interferon-free regimen of REP 2139 with TDF or ETV could improve antiviral response and shorten treatment regimens in HBV infected patients. APASL2016:在体内REP 2139-Ca和核苷(酸)类似物抗HBV治疗的抗病毒作用 |
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