Prolonged TDF monotherapy supported in multidrug-resistant HBV
medwireNews: Treatment with tenofovir disoproxil fumarate (TDF) alone is efficacious over the long term in patients with chronic hepatitis B virus (HBV) infection that is resistant to multiple antiviral agents, research indicates.
The study was a combined extension of two trials that demonstrated the noninferiority of TDF monotherapy to the combination of TDF and entecavir in patients with persistent viremia and documented resistance to entecavir or adefovir dipivoxil.
Of 192 patients enrolled in the trials, 189 completed the initial 48 weeks of the randomly assigned regimen and agreed to continue with or switch to TDF alone for a further 96 weeks, with the majority (93.8%) remaining on treatment for the full 144 weeks.
At week 48, a comparable 66.3% of patients given TDF alone and 68.0% of those who received the combination achieved a virologic response, defined as serum HBV DNA levels below 15 IU/mL.
But the overall response rate rose to 74.5% after the additional 96 weeks of TDF monotherapy, which was significantly higher than the week 48 response rate (p=0.03). There was no significant difference in response between participants who had continued with TDF and those who switched after combination therapy, with rates of 76.8% and 72.2%, respectively.
The on-treatment analysis revealed similar results, with 79.4% of 180 participants achieving a virologic response at the 144-week mark.
During the course of the study, six patients – four in the TDF–TDF and two in the TDF/ETV–TDF group – experienced virologic breakthrough, defined as increases in HBV DNA levels of at least 1 log10 IU/mL on two consecutive examinations. The breakthroughs were attributed to reduced adherence and were transient, according to the report in Hepatology.
Additionally, 19 patients had HBV DNA levels over 60 IU/mL at week 144 and qualified for genotypic resistance analysis. Despite the “suboptimal” response at week 48, which the researchers found “concerning, because persistently replicating HBV clones would be more likely to develop additional resistance mutations,” no new mutations were observed.
So Young Kwon (Konkuk University School of Medicine, Seoul, Korea) and co-investigators say that the rising response rate with prolonged TDF monotherapy and the lack of new resistance mutations is “reassuring.”
And they conclude: “Given the necessity of long-term indefinite [nucleos(t)ide analog] treatment to maintain viral suppression, and taking into consideration the lower potential risk of adverse events, lower cost, and non-inferior antiviral efficacy compared with TDF/ETV combination therapy, our data suggest that TDF monotherapy may be a proper long-term treatment option for patients with multidrug-resistant HBV.”
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