Treatment
Figure 1. Manifestations of Antiviral Resitance
Antiviral Treatment
HBV DNA (Log10 IU/mL)
ALT (U/L)
8
Virologic
Rebound
6
Virologic
Breakthrough
Hepatitis Flare
4
Biochemical
Breakthrough
Genotypic
Resistance
2
ULN
0
-1
0
1
2
3
Years
Serial changes in serum HBV DNA and ALT levels in association with emergence of
antiviral-resistant HBV mutants. The first manifestation of antiviral resistance is the
detection of resistant mutations (genotypic resistance). Resistant mutations may be
detected at the same time or prior to virologic breakthrough (increase in serum HBV
DNA by > 1 log10 above nadir). With time, serum HBV DNA levels continue to increase
(viral rebound) and ALT become abnormal (biochemical breakthrough). In some patients,
emergence of antiviral resistance leads to a marked increase in ALT (hepatitis flare).
Table 5. Management of Antiviral-Resistant HBV
Prevention
Avoid unnecessary treatment
Initiate treatment with potent antiviral that has a low rate of drug resistance or with
combination therapy
Switch to alternative therapy in patients with primary nonresponse
Monitoring
Test for serum HBV DNA (PCR assay) every 3-6 months during treatment
Check for medication compliance in patients with virologic breakthrough
Confirm antiviral resistance with genotypic testing
Treatment
Lamivudine-resistance
Add adefovir or tenofovir
Stop lamivudine, switch to Truvada�� a,b
Adefovir-resistance
Add lamivudinec
Stop adefovir, switch to Truvada�� a,b
Switch to or add entecavirb,c
Entecavir-resistance
Switch to tenofovir or Truvada�� b
Telbivudine-resistanced
Add adefovir or tenofovir
Stop telbivudine, switch to Truvada��
Truvada�� = combination pill with emtricitabine 200 mg and tenofovir 300 mg.
In HIV coinfected persons; scanty in vivo data in non-HIV infected persons.
c
Durability of viral suppression unknown, especially in patients with prior lamivudine resistance.
d
Clinical data not available.
a
b
8
