Efficacy and Tolerability of Adefovir- versus Tenofovir-based Combination Therapy Regimens in a Cohort of Individuals with Chronic Hepatitis B

The use of lamivudine (LAM) [Epivir-HBV] monotherapy is effective against chronic hepatitis B (CHB), but drug resistance eventually develops. In the current study, researchers at Mt. Sinai Medical Center in New York City evaluated the use of combination nucleoside/tide analogue (NA) therapy to maximize HBV suppression and decrease the risk of viral resistance.

The data on the use of combination therapy in HBV infection are scarce, especially involving the nucleotide tenofovir. The Mt. Sinai investigators compared the effectiveness and tolerability of tenofovir and adefovir (Hepsera) in a cohort of patients with chronic hepatitis B.

The researchers identified from the cohort database those patients receiving combination nucleoside analog (NA) treatment for a minimum of 6 months. The effectiveness of tenofovir- versus adefovir-based regimens was assessed at 6 and 12 mo on therapy. The information gathered included the number of patients who achieved undetectable HBV DNA (<160 copies/ml), time to undetectability, ALT normalization, HBeAg seroconversion, and adverse events.

Results

• Data on 30 pts were analyzed.
• 21/30 (70%) had previously received ADV or LAM monotherapy and had been switched to combination due to failure to become undetectable or viral rebound.
• 10/30 (30%) were NA-naïve.
• Median age was 35 years (23 – 68), 16/30 (53%) were Asian, 12/30 (40%) Caucasian, and 23/30 (77%) were male.
• 20/30 (67%) were HBV eAg +, all were HIV negative.
• 13 pts received TDF based regimens, (TDF + emtricitabine (FTC) n=8, TDF + LAM n=5), and 17 had ADV-based regimens, (ADV + FTC, n=4, ADV + LAM n=13).
• 13/30 (43%) had BL ALT > 2x ULN, median = 82 U/L (16 – 228).
• Median BL HBV DNA (n=29) was 1.4 x 105 cps/ml (2.0x10 2 - 2.0x10 9). Median length of therapy was 14 mos (6 – 31).
• Median time to HBV DNA < 160 cps/ml was shorter in NA-naïve v experienced pts (4.5 v 6.5 mo) but longer in HBV eAg + v eAg – pts (7 v 5 mo).
• 6/13 (69%) normalized ALT and 2 pts seroconverted from HBV eAg + to HBV eAb + during therapy.

The efficacy of TDF vs ADV based regimens is outlined in the table below.

Three patients in both ADV and TDF treatment groups achieved a mean log decrease in HBV DNA of 3.0 and 2.7 respectively, but did not fall to < 160 copies/ml. No adverse events were noted and serum creatinine was stable on therapy.

In conclusion, the study authors write, “In our cohort, ADV-based combination regimens achieved a more rapid fall in HBV DNA than TDF-based regimens. Both appear potent and well tolerated.”

“Further studies are needed to evaluate differences in efficacy between these 2 regimens.”

“Long-term follow up is required to determine if the use of combination NA therapy will decrease the incidence of drug resistance.”

11/28/05

Reference
G Y Im and others. Comparison of Tenofovir- versus Adefovir-based Combination Therapy in Subjects with Chronic Hepatitis B. Abstract 999. Abstracts of the 56^th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. San Francisco, CA.