Outcomes of HBV treatment in South Africa: How commonly does viraemia persist, and can we predict why?

Background: Nucleos(t)ide analogues (NAs) are used to suppress viraemia in people living with chronic hepatitis B virus (HBV) infection, with tenofovir disoproxil fumarate (TDF) being safe, accessible and effective for most patients. However, viraemia can be slow to suppress. We set out to determine the proportion of individuals in whom HBV viraemia is not suppressed after ≥ 12 months of NA treatment, and to identify factors associated with this phenotype in a South African cohort.

Methods: We reviewed clinical data from the ‘OxSA-Hep’ cohort, a cross-sectional cohort of 333 adults recruited from Cape Town and Bloemfontein, South Africa between 2019 and 2023. Ethics approval was provided by the University of Oxford Tropical Research Ethics Committee (OXTREC ref. 01–18), Stellenbosch University Human Research Ethics Committee (HREC ref. N17/01/013) and the University of the Free State Research Ethics Committee (HSREC ref. 203/2016). We employed non-parametric and parametric analyses in R to discern differences between those with successful virological suppression after ≥ 12 months of NA treatment, and those on treatment but ‘Not Virologically Suppressed’ (NVS; HBV DNA > 50 IU/ml after ≥ 12 months of treatment).

Results: 104/333 adults (31.2%) were on NA treatment and had detectable HBV DNA. Treatment duration and HBV DNA levels were available for 65/104 (62.5%). Among this population, median age was 42 (28 to 74 years), 27 (41.5%) were female, 25 (38.5%) had HBV mono-infection and 40 (61.5%) had HBV/HIV co-infection. 25/65 (38.5%) met our NVS criteria. There was no significant difference in sex, body weight, age, HBeAg status, alanine transaminase levels, bilirubin levels and elastography between those with and without successful viraemic suppression (p-values > 0.05). There was a significant difference in HIV status (p-value 0.02) with 20/25 (80%) of those not virologically suppressed living with HIV. 11/20 (55%) had > 1 log₁₀ difference in HBV and HIV viraemia. 9/11 (81.8%) were on TDF-based therapy and 66.7% had achieved HIV suppression (HIV RNA < 50 IU/mL) but not HBV suppression.

Conclusion: In this cohort of adults living with HBV infection, about 1 in 3 is on treatment. Among those treated for at least a year, HBV viraemia was not suppressed in 38.5%, leaving a potential risk for disease progression and transmission. Those with HBV/HIV co-infection in whom HIV viraemia is suppressed but HBV is not have a clinical phenotype suggestive of potential drug resistance.