Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load

Abstract

We evaluated the antiviral response of patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as having hepatitis B virus (HBV) DNA ≥ 9 log10 copies/mL, after 240 weeks of tenofovir disoproxil fumarate (TDF) treatment. A total of 641 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients (129 with HVL) received 48 weeks of TDF 300 mg (HVL n = 82) or adefovir dipivoxil (ADV) 10 mg (HVL n = 47), followed by open-label TDF for an additional 192 weeks. Patients with confirmed HBV DNA ≥ 400 copies/mL on or after week 72 had the option of adding emtricitabine (FTC). By week 240, 98.3% of HVL and 99.2% of non-HVL patients on treatment achieved HBV DNA <400 copies/mL. Both groups had similar rates of histologic regression between baseline and week 240. Patients with HVL generally took longer to achieve HBV DNA <400 copies/mL than non-HVL patients, but by week 96, the percentages of patients with HBV DNA <400 copies/mL were similar in both groups. Among HVL patients, time to achieving HBV DNA <400 copies/mL was shorter among those initially receiving TDF, compared to ADV. No patient with baseline HVL had persistent viremia at week 240 or amino acid substitutions associated with TDF resistance.

Conclusion: CHB patients with HVL can achieve HBV DNA negativity with long-term TDF treatment, although time to HBV DNA <400 copies/mL may be longer, relative to patients with non-HVL.

Figure 1

Time to viral negativity on the basis of baseline viral load. The proportion of patients with HBV high baseline viral load (≥9 log₁₀ copies/mL) and non-high baseline viral load (<9 log₁₀ copies/mL) who achieved HBV DNA <400 copies/mL during TDF long-term treatment. (A) Excludes patients who received FTC. (B) Includes patients who received FTC. Vertical bars represent 95% confidence intervals.

Figure 2

Viral load over time. Mean HBV DNA for patients with high baseline viral load (≥9 log₁₀ copies/mL) and non-high baseline viral load (<9 log₁₀ copies/mL) during TDF long-term treatment. (A) Excludes patients who received FTC. (B) Includes patients who received FTC. Vertical bars represent 95% confidence intervals.

Figure 3

Time to viral negativity on the basis of initial therapy. The proportion of patients with HBV high baseline viral load who reached HBV DNA <400 copies/mL after initial treatment with either TDF or ADV. (A) Excludes patients who received FTC. (B) Includes patients who received FTC. Vertical bars represent 95% confidence intervals.