Real-World Experiences with Tenofovir Disoproxil Fumarate: Is this the “B-Ticket”?

Abstract

The preferred options for treatment of chronic hepatitis B viral (HBV) infection in countries without resource constraints are peginterferon, entecavir, or tenofovir disoproxil fumarate (TDF) [1,2]. For most clinicians, peginterferon is infrequently considered due to the greater complexity of monitoring, higher frequency of adverse effects and patient preference, which narrows the treatment options to TDF or entecavir. In the registration trials of treatment-naïve patients with chronic hepatitis B, both TDF and entecavir demonstrated high rates of on-treatment HBV DNA suppression and low rates of viral resistance coupled with excellent safety [3,4]. Given that TDF and entecavir have been approved therapies for HBV for more than a decade, data derived from ''real-world'' cohort studies have helped fill knowledge gaps regarding the use of these drugs in clinical practice. In the case of TDF, the issues of particular interest include: (1) the efficacy of TDF across a wider spectrum of patients including those less adherent than patients in clinical trials, and (2) the risks associated with longer-term use of TDF, especially the frequency of viral resistance and the risk of renal and bone toxicity.Patients participating in clinical trials are a select group-typically healthier than many patients in the clinic, with fewer comorbidities and higher rates of adherence. The registration trials for TDF required a estimated glomerular filtration rate (eGFR) [70 ml/min, absence of anemia, neutropenia, and liver decompensation or presence of unstable comorbidities [3]. In practice, patient complexity can be greater, comorbidities not always optimized, and adherence less assured. Understanding how antivirals perform under these less than ideal circumstances is important. The ideal ''real-world'' study would prospectively enroll consecutive patients and account for all patients at study end, provide intent-to-treat as well as perprotocol analyses, and include details of treatment failures, including reasons for treatment discontinuation. The ''realworld'' cohorts included in this issue of Digestive Diseases and Sciences-GEMINIS from Germany [5] and VIREAL from France [6]-partially meet these high standards. Regardless, some important practical messages can be gleaned from their analyses.The VIREAL and GEMINIS cohorts enrolled [800 patients from diverse practice settings who were newly initiated on TDF therapy [5,6]. Treatment-naïve and experienced subjects were included, with a substantial proportion of the treatment-experienced patients transitioning from another nucleos(t)ide analog therapy to TDF and having low or undetectable HBV DNA levels at the time of TDF initiation. Hypertension, diabetes, renal disease, cardiovascular diseases, and other comorbidities were present in *40 % of patients [5] with up to 28 % having eGFR \90 ml/min [6]. Although the intent of the study was to follow patients for 3 years, both cohorts suffered from patient attrition, leading to incomplete reporting of virologic and safety data. The primary...