A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) genotypic resistance in people treated with entecavir or tenofovir

Abstract

AbstractBackgroundAs nucleos/tide analogue (NA) therapy for chronic Hepatitis B virus (HBV) infection becomes more widely indicated and available, understanding drug resistance is essential. We performed a systematic review and meta-analysis to estimate the risk of genotypic resistance to tenofovir and entecavir.MethodsWe searched nine databases up to 29-Aug-23. We included studies of HBV infection featuring >10 individuals, written in English, reporting tenofovir or entecavir treatment ≥48 weeks, with assessment of HBV genotypic resistance. Data were analysed according to prior exposure history to NA, and treatment with tenofovir or entecavir. Analyses were performed in R.Results62 studies involving a total of 12,358 participants were included. For tenofovir, pooled resistance risk was 0.0% at all time points, whether previously NA naive (11 studies; 3778 individuals) or experienced (19 studies; 2059 individuals). For entecavir, in treatment-naive individuals (22 studies; 4326 individuals), risk of resistance increased over time to 0.9% at ≥5 years (95%CI 0.1-2.3%). Entecavir resistance was increased in NA-experienced individuals (18 studies;1112 individuals), to 20.1% (95%CI 1.6-50.1%) at ≥5 years. There was a lack of consistent definitions, poor global representation and insufficient metadata to support subgroup analysis.DiscussionBased on existing data, tenofovir has an excellent resistance profile. More resistance is seen with entecavir, particularly in treatment-experienced groups. Due to data gaps, we may have under-estimated the true risk of resistance. Robust prospective data collection is crucial as treatment is rolled out more widely.