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ATI-2173 + tenofovir disoproxil fumarate is a combination investigational therapy for chronic hepatitis B virus (HBV) infection. ATI-2173 is a novel oral, liver-targeted Active Site Polymerase Inhibitor Nucleotide (ASPIN) designed to deliver clevudine monophosphate to the liver, where it is converted to the active triphosphate form, functioning as a noncompetitive, non-chain terminating inhibitor of HBV polymerase[1][2][5][7]. This distorts the HBV polymerase active site, resulting in potent antiviral activity and sustained suppression of viral DNA. Tenofovir disoproxil fumarate is a nucleotide analog reverse transcriptase inhibitor (nRTI) that acts as a chain terminator of HBV DNA synthesis and is approved for hepatitis B and HIV-1 management[3][6]. The combination targets complementary mechanisms in HBV DNA replication, with ATI-2173 inhibiting the active site and tenofovir inducing chain termination. Clinical studies demonstrate that the combination is generally well-tolerated, leading to potent HBV DNA suppression, ALT normalization, and decline in cccDNA activity biomarkers[4][7]. The regimen is being developed by Antios Therapeutics for potentially curative and safer treatment options for chronic HBV infection[2][7].
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