by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
July 16, 2024
Featured Literature:
Lumley SF, Delphin M, Mokaya JF, et al. A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) resistance in people treated with entecavir or tenofovir. J Clin Virol. 2024 Jun 28; 174:105711.
Investigators sought to establish entecavir or tenofovir resistance estimates among people receiving treatment for hepatitis B. English-language original research studies were included if they involved ten or more people with chronic HBV exposed to tenofovir (TFV) and/or entecavir (ETV) monotherapy for 48 or more weeks, and reported risk of clinical and genotypic resistance. Studies were excluded if investigators were unable to separate naïve from experienced outcomes. 62 studies involving 12,358 participants were included. Among 24 studies of nucleos/tide analogue (NA) naïve people receiving ETV, a low risk of resistance was observed which increased with treatment duration, from 0.0% after 1 year to 0.9% at/after 5 years. Among 18 studies of NA experienced people receiving ETV, resistance was common and again increased over time, from 0.2% at 1 year to 20.1% at/after 5 years. Among 11 studies of NA naïve people receiving TFV, pooled estimates were 0.0% across all time points (95% CI range 0.0%-0.2%). Similarly, among 22 studies of NA experienced people treated with TFV, pooled estimates were 0.0% at all time points (95% CI range 0.0%-2.2%). In this group of studies, emergent RAMs were described in two people (two emerged in one participant, one emerged in the other).
Author’s Commentary:
As HBV screening and treatment guidelines continue to expand across the globe, and options for therapeutic interventions evolve, a closer understanding of the risk factors for (and prevalence of) antiviral therapy resistance is necessary to inform clinical management, methodologic standardization for laboratories and interpretation systems, and population health approaches. Authors acknowledge a number of limitations with this review (e.g., most studies were from relatively resource-rich settings and there was notable clinical and methodological heterogeneity especially for studies involving NA experienced populations). They also provide a “call to action” which emphasizes global representation in future investigations, standardized reporting of drug resistance, and increased data sharing to “guide strategies for implementation of effective therapy that will support progress towards HBV elimination worldwide.”
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