Associate Professor of Medicine
University of Toronto
Toronto Centre for Liver Disease
Sandra Rotman Centre for Global Health
Jordan J. Feld, MD, MPH, has disclosed that he has received consulting fees from AbbVie, ContraVir, Gilead Sciences, Janssen, and Merck and funds for research support from Abbott, AbbVie, Gilead Sciences, Janssen, and Merck.
When deciding among first-line HBV treatments, we have 3 potent, safe options with high barriers to resistance: entecavir, tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF). I would consider any of these to be a good choice for most patients. However, there are a few key clinical scenarios where I would recommend a specific agent over the others.
Given the potential renal complications with long-term TDF, I would narrow the options to entecavir or TAF in patients with renal disease or renal risk factors (eg, older patients and/or those with hypertension or diabetes). Deciding between these 2 agents depends on the severity of the renal disease.
For those with end-stage renal disease on dialysis, I would select entecavir because it has dosing recommendations for that setting. By contrast, TAF is not recommended for individuals with an estimated creatinine clearance < 15 mL/min.
For those at risk for renal disease or with mild or moderate renal impairment, an advantage of TAF is that there are no dose adjustments above that estimated creatinine clearance of 15 mL/min. It is helpful when you do not need to recalculate renal function and make dosing adjustments.
Based on short-term data, we expect the antiviral efficacy, resistance profile, and safety benefits in terms of renal and bone toxicity to be as good or better with TAF than with TDF or entecavir. However, it is worth noting that we lack the long-term experience that we have with entecavir and TDF.
We are also waiting for more data to be collected on TAF in settings of decompensated cirrhosis and pregnancy, as well as in children. Outside of a clinical trial, in these 3 populations, TDF would likely be preferred over TAF because of the larger body of evidence of TDF.
To see which agent would be recommended by 5 experts in various settings involving renal dysfunction, please visit Clinical Care Option’s decision support tool for first-line HBV therapy.
Availability and Cost
For patients without medical reasons to choose one agent over another, the choice of agent may depend on drug availability, insurance coverage, and cost. More rarely, drug–drug interactions can present issues that compel selecting an agent over the others.
Counterintuitively, generic agents may sometimes be more expensive if the manufacturer does not cover the patient’s copay. That can sometimes be burdensome and a good reason to select another agent where the copay is lower or completely covered.
Duration of Therapy
Although finite therapies for HBV are under development, we currently assume that most patients will be on treatment long term to indefinitely. When selecting a first-line agent, should we factor in the potential safety issues associated with long-term exposure (eg, bone and renal complications with long-term TDF)?
For example, when I am recommending initial HBV treatment for a healthy 30-year-old person with no comorbidities, I do not consider whether they may develop hypertension and diabetes in the future—the risk for complications with TDF vs TAF or entecavir is not a factor in such a patient. Instead, my plan is to address those issues if they arise later in the patient’s life.
When have you strongly recommended one of these 3 agents over the others? Do you consider a young, healthy patient’s risk for long-term complications when recommending a first-line therapy? Please share your thoughts in the comments box.