Development of tenofovir disoproxil fumarate resistance after complete viral suppression in a patient with treatment-naïve chronic hepatitis B: A case report and review of the literature

Abstract

Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue that is recommended as first-line therapy for patients with chronic hepatitis B. The results of a longitudinal study of TDF treatment demonstrated no development of resistance. We observed one treatment-naïve chronic hepatitis B (CHB) patient who developed TDF resistance after complete viral suppression during long-term TDF treatment. A 37-year-old HBeAg-positive man received TDF 300 mg/d for 43 mo. The hepatitis B virus (HBV) DNA titer was 8 log10 copies/mL at baseline and became undetectable at 16 mo after treatment. However, the HBV DNA titer rebounded to 7.5 log10 copies/mL at 43 mo after treatment. We performed full sequencing to find mutation sites associated with virologic breakthrough. The results showed 9 mutation sites, most of which had not been well-known as mutation sites. We changed the therapy from tenofovir to entecavir with a regimen of 0.5 mg once daily. After 4 mo, the HBV DNA titer decreased to 267 copies/mL, and the liver enzyme levels were normalized.

Harnessing host–virus evolution in antiviral therapy and immunotherapy

“…Tenofovir is an example of a highly effective single‐regimen treatment for chronic hepatitis B infection, a retro‐transcribing virus characterised by considerable genetic heterogeneity, by simultaneously imposing potent viral suppression, a high barrier for escape and reduced replicative fitness of escape strains. Despite these synergising effects, complex escape mutants harbouring multiple point substitutions in the viral reverse transcriptase have recently emerged . One way of enhancing treatment efficacy while minimising viral escape is to deploy existing antivirals as combination therapies, a strategy used extensively in current HIV (e.g.…”

Interferon alpha treatment leads to a high rate of hepatitis B surface antigen seroconversion in Chinese children with chronic hepatitis B

“…Moreover, similar to HIV, HBV can potentially evolve resistance to NAs if the drugs are not taken correctly and regularly. In fact, an HBV variant resistant to TDF, one of the most potent HBV antivirals available, recently emerged . If HBV develops resistance to NAs in early life, the patient will lose the opportunity to effectively control virus replication and prevent progression to liver morbidity.…”

“…In fact, an HBV variant resistant to TDF, one of the most potent HBV antivirals available, recently emerged. 15,16 If HBV develops resistance to NAs in early life, the patient will lose the opportunity to effectively control virus replication and prevent progression to liver morbidity. For these reasons, the use of NA drugs in children is generally restricted and only recommended in special circumstances.…”

Hepatitis B and Pregnancy: Virologic and Immunologic Characteristics

“…The impact of short‐term TDF use in multiple gestations is unclear because most studies (especially in China) were conducted in women with single pregnancies. Recently, TDF‐resistant mutants were identified in a treatment‐naive Chinese patient with CHB . The potential risk of reselection of resistant variants by repeat TDF exposure is unknown but predicted to be extremely rare.…”