Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study

Abstract

The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240weeks. Clinical trial number: NCT00737568.

Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance

“…In phase III clinical trials of TDF, there was no evidence of TDF resistance among 641 NA‐naïve patients who received TDF for up to 8 years, and most cases of virological breakthrough were attributed to nonadherence . Similarly, in another study of 280 patients with lamivudine resistance who received TDF alone or in combination with emtricitabine for up to 240 weeks, TDF resistance was not found . Although long‐term data on risk of resistance with TAF are lacking, no resistance has been reported in clinical trials with 2‐year follow‐up …”

“…In vitro studies showed that susceptibility of adefovir‐resistant HBV, with a single N236T or A181V/T mutation, to TDF is minimally changed compared with wild‐type HBV, but susceptibility is lower when both mutations are present. Clinically, most studies have found that TDF is effective in suppressing adefovir‐resistant HBV without any benefit from adding emtricitabine …”

“…Based upon virological principles, the risk of viral resistance is predicted to be lower with combination antiviral therapy compared with monotherapy. Comparative evidence with follow‐up to 5 years suggests monotherapy achieves rates of HBV DNA suppression comparable to those of combination therapy when antivirals such as tenofovir are used Although the optimal frequency of HBV‐DNA monitoring has not been fully evaluated, monitoring of HBV‐DNA levels every 3 months until HBV DNA is undetectable and then every 3‐6 months thereafter allows for detection of persistent viremia and virological breakthrough. For persons on treatment with NAs other than tenofovir or entecavir, viral breakthrough warrants a switch to another antiviral monotherapy with a high genetic barrier to resistance or the addition of a second antiviral with a complementary resistance profile (Table ). …”

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…In addition, studies using sensitive markers of glomerular and tubular kidney function and of bone mineral density have also reported chronic tubular damage and decline of eGFR and bone mineral density in TDF treated patients. 70,[79][80][81][82][83][84][85][86][87] Therefore, it seems appropriate for now to monitor all CHB patients treated with TDF therapy for adverse renal effects with serum creatinine (eGFR) and serum phosphate levels. Moreover, CHB patients at high renal risk undergoing any NA therapy should be monitored with serum creatinine (eGFR) levels.…”

Okuda lecture: Challenges of hepatitis B in the era of antiviral therapy

“…In another randomized trial among HBeAg‐positive patients with HBV‐DNA > 7 log IU/mL and normal alanine aminotransferase, 69.4% of patients on TDF combined with emtricitabine versus 45.3% patients on TDF monotherapy could achieve HBV‐DNA < 29 IU/mL . However, in patients with drug resistance, most evidence suggests that combination therapy, either combining TDF with entecavir or combining TDF with emtricitabine, will not increase the chance of complete viral suppression …”