Despite the high diversity of hepatitis C virus (HCV) across Africa, direct-acting antiviral (DAA) combinations provide high rates of sustained virological response (SVR), except for HCV subtypes gt1l and gt4r, according to study results published in The Journal of infectious Disease.
Chronic HCV infection predominantly affects individuals living in lower- and middle-income countries. DAA therapies provide a higher range of SVR in high-income countries where the range of HCV genotypes and subtypes are more limited.
To examine the effectiveness of DAA in individuals from lower- or middle- income countries, a team of investigators conducted an analysis of UK residents with HCV who were born in Africa. The researchers aimed to address treatment outcomes in this patient population, as well as to provide additional complete HCV genomic sequences of African patients, as data for this demographic is currently lacking.
A total of 319 patients from 32 African countries were included in the analysis; 66.5% of participants were men, the average patient age was 59 years (range, 24-88 years), and 131 patients had cirrhosis (no decompensation, n=53; decompensation, n=42; hepatocellular carcinoma [HCC], n=25; decompensation with HCC, n=11). In addition, the majority of patients reported their probable source of infection as being born abroad (40%), followed by blood or blood products (17%), and injection drug use (10%).
Using next generation sequencing of samples from 233 patients, researchers generated sequence data for the entire HCV coding region. Following unsuccessful DAA therapy, viral sequence data was collected for an additional 14 samples. Overall, the investigators identified 7 gt1 subtypes, 3 gt2 subtypes, 2 gt3 subtypes, 13 gt4 subtypes, and 2 gt5a sequences.
Study authors evaluated treatment outcomes for all DAA drug combinations used for this patient population. Data was collected for 149 patients (162 recorded treatment episodes). The overall SVR was 93% for these patients.
Results of a univariate analysis suggested that HCC and decompensated cirrhosis were associated with failure of DAA therapy (P=.006; P=.061, respectively). In addition, treatment failure was also associated with use of sofosbuvir/ledipasvir in patients with subtypes gt1l and gt4r; SVR for the other gt1 and gt4 subtypes was 97%.
“These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination,” the authors noted.
“Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommend treatment option,” the study authors concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Aranday-Cortes E, McClure CP, Davis C, et al. Real-world outcomes of DAA treatment and retreatment in UK-based patients infected with HCV genotypes/subtypes endemic in Africa. J Infect Dis. Published online March 1, 2021. doi:10.1093/infdis/jiab110