Eligibility for hepatitis B virus (HBV) treatment and prevalence of drug resistance in a Ugandan population cohort.

BackgroundThe World Health Organization (WHO) 2024 Hepatitis B virus (HBV) treatment guidelines expand eligibility for nucleos(t)ide analogue treatment in individuals with chronic HBV infection. For countries to implement these guidelines, there is a critical need to understand the population who are treatment eligible. While HBV drug resistance (HBVDR) is uncommon, monitoring for any potential resistance is a relevant public health consideration. MethodsWe studied a population in rural Uganda to describe the proportion of individuals eligible for treatment based on the 2024 WHO treatment guidelines. We determined how this proportion varies according to the eligibility criteria used, comparing the performance of different assessment tools. We calculated Aspartate Aminotransferase-to-Platelet Ratio Index; APRI, Gamma-Glutamyl Transpeptidase-to-Platelet Ratio; GPR and transient elastography; TE and performed HBV sequencing using Oxford Nanopore Technology to determine the prevalence of HBVDR in treatment naive and treatment experienced individuals. ResultsIn this cohort, 24/63 (38%) individuals with CHB were eligible for treatment. This fell to 14/63 (22%) in a hypothetical scenario where TE was not available for the assessment of liver fibrosis. We demonstrate a lack of concordance between non-invasive tests (NIT) of liver disease in treatment-naive HBV mono-infected individuals. An APRI cut-off of 0.5 had a sensitivity of 23.0% for predicting a TE score of >7 kPa (F2 fibrosis). Sensitivity for detecting F2 fibrosis was increased to 38.5% using an APRI cut off of 0.36, and to 46.2% using the GPR. We did not identify any HBVDR in the HBV mono-infected treatment-naive population (n=58). 24/210 individuals were living with HIV/HBV coinfection; HBV was sequenced in 5 of these of whom 2 had genomic evidence of nucleos(t)ide analogue resistance (rt180M/204V). ConclusionsWhile the WHO 2024 treatment criteria offer an opportunity to expand access to care, there is a need to determine how assessment tools differ in determination of eligibility in different settings. HBVDR remains uncommon but more research is needed to understand its prevalence and clinical impact in African populations.