Resistance to prior antiviral agents impacts TDF response

Mar 10 2016

By Shreeya Nanda

Taiwanese researchers find that virological response to tenofovir disoproxil fumarate (TDF) in treatment-experienced patients with chronic hepatitis B virus (HBV) infection can vary depending on the nucleos(t)ide analogue (NA) the patient is resistant to.

Their chart review included 236 chronic HBV patients who had received TDF therapy for at least 12 months - of these, 131 had not received prior NA therapy while the remaining 105 had. Of the latter, 66 exhibited resistance to a previous antiviral agent or a suboptimal response to entecavir.

At 36 months, the cumulative rate of virological response - defined as serum HBV DNA levels lower than 20 IU/mL - was comparable between NA-naïve patients (97.7%), NA experienced patients without drug resistance (100.0%) and those with resistance to either lamivudine or telbivudine (100.0%).

However, the cumulative virological response rate at this timepoint for patients with adefovir-resistant infection and those with a suboptimal response to entecavir was significantly lower than for NA-naïve patients, at 58.3% (p=0.003) and 90.0% (p=0.003), respectively, versus 97.7%.

Moreover, participants with a suboptimal response to entecavir were also significantly less likely compared with NA-naïve patients to achieve loss of hepatitis B e antigen, with cumulative rates at 36 months of 7.1% versus 58.5% (p=0.003).

Writing in the Journal of Gastroenterology and Hepatology, the researchers highlight, however, that the number of patients with adefovir-resistant HBV (n=6) was limited.

They also assessed the safety profile of single-agent TDF and found that in the overall study population the average estimated glomerular filtration rate (eGFR) decreased markedly from baseline to 6 months and from 6 to 12 months, but then remained stable until study end.

These changes in mean eGFR were driven mainly by the subgroup of patients with a baseline eGFR of at least 90 mL/min per 1.73 m², says the team, as mean values for those with an initial eGFR below 90 mL/min per 1.73 m² did not change significantly during TDF therapy.

Furthermore, during the study, 17.8% of patients experienced a greater than 20% decrease in eGFR from baseline, with age and diabetes mellitus among the factors that independently predicted this decline.

But Chien-Hung Chen (Kaohsiung Chang Gung Memorial Hospital) and study authors admit that they "could not differentiate nephrotoxicity due to TDF from co-incidental [diabetes mellitus] nephropathy."

They add, however, that their findings suggest that renal function impairment mainly occurs in patients with comorbid conditions and recommend monitoring of renal function in such patients during treatment with TDF.

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