Patients with adefovir-resistant HBV benefit from TDF monotherapy

Apr 29 2015

By Shreeya Nanda, Senior medwireNews Reporter

Tenofovir disoproxil fumarate (TDF) alone elicits a response comparable to that of TDF plus entecavir in heavily pretreated patients with chronic hepatitis B virus (HBV) infection resistant to adefovir dipivoxil (ADV), research suggests.

“Given the necessity of long-term, almost indefinite [nucleos(t)ide analogue] treatment to maintain viral suppression, our data suggest that TDF monotherapy may be a reasonable option for the treatment of patients resistant to multiple drugs including ADV”, says the team from the Republic of Korea.

In this multicentre trial, 102 chronic HBV patients with genotypic resistance to ADV were randomly assigned to receive either open-label TDF alone (n=50) or in combination with entecavir (n=52) for 48 weeks, after which patients in the combination therapy group all received TDF only.

Virological response, defined as HBV DNA levels below 15 IU/mL, at week 48 was achieved by a comparable proportion of patients in the monotherapy and dual therapy arms, at 62.0% versus 63.5%. This was also the case at week 96, with a response rate of 64.0% and 63.5%.

There was also no significant difference between the groups at either time point with respect to the mean change from intake in serum HBV DNA levels or the proportion of patients with HBV DNA levels less than 60 IU/mL or those achieving alanine aminotransferase normalisation.

When patients were stratified by the number of ADV-resistant mutations, once again the treatment arms were similar in terms of virological response rate at weeks 48 and 96, both for patients with single and those with double mutations.

But in participants harbouring double, but not single, mutations, the team did observe a nonsignificant trend towards a smaller decrease in serum HBV DNA levels at week 48 in the TDF alone group than in the TDF plus entecavir group. Noting the small number of patients with double mutations in their study, the researchers say that “further larger-scale studies are warranted”.

Virological breakthrough, defined as an elevation in HBV DNA levels of at least 1 log₁₀ IU/mL from nadir on two consecutive tests, occurred in one patient given TDF monotherapy and in two patients who received dual therapy – the researchers attribute these incidences to reduced medication adherence.

Highlighting that TDF alone and together with entecavir was “well tolerated” over the 96-week period, joint senior investigators Young-Suk Lim (University of Ulsan College of Medicine, Seoul) and Byung Chul Yoo (Sungkyunkwan University School of Medicine, Seoul) and co-authors reiterate that TDF monotherapy could be a treatment option for this particular patient population.

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