TABLE 3.

Antiviral therapeutics for chronic hepatitis B

DrugaMechanism of actionbEfficacycResistance
IFN-αImmune-mediated clearanceHBeAg+ CHB: 20% greater VR, 6% greater CR than untreated controls (150)None
HBeAg CHB: avg 24% SR-12 vs 0% for untreated controls (91)
Pegylated IFN-α2a and IFN-α2b*Immune-mediated clearanceHBeAg+ CHB: 10% greater BR and VR at 6 mo posttreatment than with lamivudine (13, 79); pegylated IFN-α2a and IFN-α2b similarly efficacious (60, 79)None
HBeAg CHB: 15% greater BR and VR 6 at mo posttreatment than with lamivudine (95)
No added benefit of combined pegylated IFN plus lamivudine for HBeAg+ or HBeAg CHB (60, 79, 95)
LamivudineNRTI; cytidine analog12-mo regimen: BR and VR at 12 mo posttreatment 10-15% greater than untreated controls for HBeAg+ and HBeAg CHB (46, 91)HBeAg+ and HBeAg CHB: 1 yr, 20%; 2 yr, 40%; 3 yr, 60%; 4-5 yr, 70% (18, 80, 115)
Prolonged treatment: HBeAg seroconversion rates progressively increase to 50% after 5 yr in HBeAg+ CHB; BR and VR peak after 24-36 mo (∼50%) and then decline in HBeAg CHB (91)
Adefovir dipivoxilNRTI; dATP analog (chain terminator)HBeAg+ CHB (end of treatment): VR, ∼20%; BR, ∼50% (compared to placebo) (94)HBeAg+ and HBeAg CHB: 1 yr, 0% (47, 149)
HBeAg CHB: VR, 70%; BR, 40% (47)HBeAg CHB: 2 yr, 3%; 3 yr, 6% (47); 5 yr, 29% (48)
Entecavir2′-Deoxyguanosine analog; inhibits polymerase priming activity and chain elongationHBeAg+ CHB: higher rates of undetectable DNA by PCR at end of treatment than with lamivudine; HBeAg loss, seroconversion, and BR equivalent to that with lamivudine (17) HBeAg CHB: higher rates of undetectable DNA by PCR at end of treatment than with lamivudine; BR equivalent to that with lamivudine (75)HBeAg+ and HBeAg CHB: 1 yr, 0% (17, 75); lamivudine-resistant strains have reduced susceptibility in vitro (155) and in vivo (28)
TelbivudineNRTI; dTTP analogNot yet published in peer-reviewed literatureHigh-level cross-resistance to lamivudine in vitro (155)
Tenofovir disoproxil fumarateNRTI; dATP analog (chain terminator)HIV-1/HBV coinfection: undetectable DNA by PCR in 30-75% of patients (8, 73)1 yr, 0% (30)
HBV monoinfection: undetectable DNA by PCR in 80-100% of patients (72, 141)
EmtricitabineNRTI; nucleoside analog of cytidineImproved histology, higher rates undetectable DNA by PCR, normalized ALT compared to controls (83); approved for use with HIV-1; may be useful in HIV-1/HBV coinfection (133)1 yr, 13% (83); 2 yr, 18% (42); high-level cross-resistance to lamivudine in vitro (155)
  • a *, IFN-α2b is not currently FDA approved for treatment of chronic hepatitis B.

  • b NRTI, nucleoside reverse transcriptase inhibitor (causes chain termination).

  • c VR, virologic response (decrease in serum HBV DNA level to <1 × 105 copies/ml and loss of HBeAg in patients with HBeAg+ CHB); CR, complete response (combined virologic response, biochemical response, and loss of HBsAg); SR-12, sustained response 12 months after therapy cessation; BR, biochemical response (normalization of ALT).