Tenofovir (TDF) has stronger antiviral effect than adefovir (ADV) against lamivudine (LAM)-resistant hepatitis B virus (HBV)

We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that of adefovir dipivoxil (ADV) for patients with chronic hepatitis B (CHB) who developed resistance to lamivudine (LAM).

One hundred nine patients (86 males), all Asian-American except 1 Caucasian male, with LAM resistance received TDF or ADV. HBV DNA levels were measured every 3 months. The HBeAg loss and ALT normalization were assessed at 12 months on therapy.

Forty-four patients (37 males) received TDF (12 with LAM) and 65 (49 males) received ADV (18 with LAM). Median ages (years) for TDF and ADV were 49 (32–68) and 45 (22–68), respectively. Median duration of therapy was 13 months (6–38) and 17 months (6–34) for the TDF and ADV groups. Baseline HBV DNA levels (log₁₀ copies/ml) were 6.2 ± 1.7 for the TDF and 6.5 ± 1.6 for ADV groups. Baseline ALT (IU/l) levels were 77.0 ± 86.0 and 100 ± 195 for the TDF and ADV (P = 0.46) groups, respectively. At 12 months, mean levels of log₁₀ HBV DNA were 1.5 ± 1.0 and 4.3 ± 2.2 for TDF and ADV (P = 0.01). HBeAg loss and ALT normalization at 12 months showed no differences. Using a single factor, ANOVA (2-tailed P value), 4 groups, TDF (n = 32), TDF + LAM (12), ADV (47), and ADV + LAM (18), were compared. HBV DNA reduction at 12 months was the greatest for TDF + LAM (P < 0.001).

Our results suggest that for LAM-resistant HBV, TDF, alone or combined with LAM exerts greater viral reduction than ADV. However, no difference in HBeAg loss was observed. It appears that stronger HBV DNA reduction may not necessarily accelerate HBeAg loss.