Despite the great diversity of hepatitis C virus (HCV) across Africa, DAA combinations provide high rates of sustained virological response (SVR), except for the two HCV subtypes gt1l and gt4r, according to the results of The study published in Journal of Infectious Diseases.
Chronic infection with hepatitis C virus mostly affects individuals who live in low- and middle-income countries. DAA treatments provide a higher range of SVR in high-income countries where the range of HCV genotypes and subtypes is more limited.
To study the effectiveness of DAA in individuals from low or middle income countries, a team of researchers conducted an analysis of UK residents with hepatitis C virus who were born in Africa. The researchers aim to address treatment outcomes in this patient population, as well as provide additional, complete genome sequencing of hepatitis C virus to African patients, as data for this demographic is currently unavailable.
A total of 319 patients from 32 African countries were included in the analysis. 66.5% of participants were men, mean patient age was 59 years (range, 24-88 years), and 131 patients had cirrhosis (decompensated, n = 53; decompensated, n = 42; HCC). [HCC], n = 25; Decompensation with HCC, n = 11). In addition, the majority of patients reported their likely source of infection as having been born abroad (40%), followed by blood or blood products (17%), and injecting drug use (10%).
Using next-generation sequencing of samples from 233 patients, the researchers generated sequence data for the entire HCV coding region. After unsuccessful DAA treatment, viral sequence data for an additional 14 samples were collected. Overall, the investigators identified 7 gt1 subtypes, 3 gt2 subtypes, 2 gt3 subtype, 13 gt4 subtype, and 2 gt5a sequences.
The study authors evaluated treatment outcomes for all DAA drug combinations used for this group of patients. Data were collected for 149 patients (162 recorded treatment episodes). The total SVR was 93% for these patients.
The results of the univariate analysis suggested that hepatocellular carcinoma and decompensated cirrhosis were associated with DAA treatment failure (s= .006; s= .061 respectively). In addition, treatment failure was also associated with the use of sofosbuvir/ledipasvir in patients with gt1l and gt4r subtypes; The SVR for the other gt1 and gt4 subtypes was 97%.
The authors noted, “These subtypes contain natural variants associated with resistance that likely contribute to poor efficacy with this drug combination.”
The study authors concluded, “In circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended therapeutic option.”
Disclosure: Several study authors have stated their association with the pharmaceutical industry. Please see the original reference for a full list of author disclosures.
Aranday-Cortes E, McClure CP, Davis C et al. Realistic outcomes of DAA treatment and retreatment in UK resident patients infected with HBV genotypes/subtypes endemic to Africa.. J infect dis. Published online March 1, 2021. doi: 10.1093/infdis/jiab110