GLS4 + ritonavir + tenofovir alafenamide

GLS4 + ritonavir + tenofovir alafenamide is a combination antiviral regimen composed of three agents with complementary mechanisms, considered for the treatment of chronic hepatitis B virus (HBV) infection and potentially HIV co-infection. **GLS4** is a novel, investigational small-molecule hepatitis B core protein allosteric modulator that interferes with viral capsid assembly. **Ritonavir** is a protease inhibitor primarily used as a potent inhibitor of CYP3A4 to boost pharmacokinetics of other antivirals. **Tenofovir alafenamide** is a prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor targeting HBV DNA polymerase and HIV reverse transcriptase. The combination is under investigation for management of HBV, particularly drug-resistant or refractory cases, potentially improving antiviral potency and resistance profiles. Development status for the triple combination is in phase 2 for HBV, sometimes tested in trials for multi-drug resistant HBV.