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To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts &lt;200 cells/μL was independently associated with persistent HBV viraemia, aOR 5.276 (95% CI 1.575–17.670) p = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing.

Persistent Hepatitis B Viraemia with Polymerase Mutations among HIV/HBV Co-Infected Patients on HBV-Active ART in KwaZulu-Natal, South Africa