Tenofovir-based salvage therapy has long-term benefits in chronic hepatitis B
medwireNews: Long-term tenofovir disoproxil fumarate (TDF) salvage therapy is effective for patients with chronic hepatitis B virus (HBV) infection who have previously failed to respond to lamivudine (LAM) and adefovir dipivoxil (ADV), 5-year TDF-109 study data show.
“There was a steady decline in serum HBV DNA levels and maintenance of viral suppression at 5 years in all compliant patients in this study, irrespective of the detection of drug-resistant mutants,” say Lucy Lim (Austin Health, Melbourne, Victoria, Australia) and colleagues.
Among 60 LAM-resistant patients with chronic HBV who failed to respond to at least 6 months of ADV add-on or switch therapy, 59 were switched to TDF monotherapy or TDF plus LAM and completed 2 years of treatment before being rolled over into the current 5-year follow-up study.
Fifty-four of the patients completed 5 years of treatment, at which time 83% had undetectable HBV DNA (lower limit of quantification <20 IU/mL), increasing from 70% at 3 years and 76% at 4 years. The median time to achieve undetectable levels was 15 months.
Overall, including the four patients who did not complete 5 years of treatment – two discontinuations, two lost to follow-up, and one death – the rate of viral suppression was 75%.
The treatment was well tolerated with few side effects and no evidence of long-term decline in renal function. There were three cases of hepatocellular carcinoma, two of which were successfully treated without the need for TDF discontinuation, while one patient infected with genotype A virus died at 28 months.
The researchers note in Liver International that the nine patients whose HBV DNA remained detectable over the 5-year period nevertheless achieved very low HBV DNA levels, no higher than 264 IU/mL and did not meet criteria for virologic breakthrough. Six also had undetectable HBV DNA levels at some stage.
Four of the nine patients had mutations linked to reduced TDF sensitivity; three at baseline and one who was infected with wild-type virus and then selected for rtA181T/N236T resistant substitutions by year 1.
None of these patients developed typical breakthrough viremia, however, so “despite the cross-resistance between ADV and TDF observed in vitro, TDF is effective in controlling viraemia in the long-term in patients with genotypic ADV resistance,” the researchers comment.
Indeed, they report that although patients carrying the ADV-resistant genetic mutation HBV rtA181T at baseline had a tendency to take longer to achieve undetectable HBV DNA levels (24 vs 10.5 months) than other patients, baseline resistance mutations had no significant effect on viral suppression.
Only a higher baseline HBV DNA load and an HBV genotype of B, C, or D relative to A were associated with a significantly longer time to HBV DNA undetectability (p<0.001 and p=0.012, respectively).
“These findings confirm that TDF has a high genetic barrier to resistance and should be the preferred oral anti-HBV agent in patients with [chronic hepatitis B] who failed treatment with LAM and ADV,” the researchers conclude.
By Lucy Piper
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