Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir–sofosbuvir (SHARED): a single-arm trial

DAA failures in African patients with “unusual” HCV subtypes: Hey! Didn’t you know there was another world?

“…6 This overrepresentation of subtype 4r among patients failing to achieve SVR was in keeping with a Rwandan study showing an SVR rate of only 56% in patients infected with subtype 4r treated with sofosbuvir/ledipasvir, significantly lower than the 93% SVR rate in patients infected with other genotype 4 subtypes. 8 Low SVR rates in patients infected with genotype 4r receiving sofosbuvir and an NS5A inhibitor were explained by the presence at baseline of multiple NS5A RASs (L28M/V + L30R ± L31M), conferring substantially reduced susceptibility to NS5A inhibitors, and of fit viral populations harboring S282C/T RASs in their polymerase sequence, conferring reduced susceptibility to sofosbuvir. 6 The implementation of the most recent pangenotypic regimens did not solve the issue: our laboratory is now receiving samples from patients of African origin infected with unusual subtypes of genotypes 1, 2 or 4 who carried NS5A RASs on their baseline genome sequences and failed to achieve SVR after sofosbuvir/velpatasvir or glecaprevir/ pibrentasvir (unpublished).…”

Epidemiology of Liver Cancer in Africa: Current and Future Trends

“…123 However, a recent study has shown far fewer SVRs among Rwandans with genotype 4r (SVR ¼ 56%). 124 Some Africans with nonsubtypable genotypes G1 and G4 have also shown unacceptably low SVRs of 73% and total failure, respectively. If confirmed, these observations may have important implications for the choice of DAA regimens to achieve elimination of hepatitis C in Africa.…”

“…If confirmed, these observations may have important implications for the choice of DAA regimens to achieve elimination of hepatitis C in Africa. 124 An interesting area beckoning research in Africa is the area of the gut-liver axis and its interaction with aflatoxicosis. Studies have demonstrated the role of gut dysbiosis in hepatic carcinogenesis with some research focusing on the interplay between the microbiome and aflatoxin.…”

Is resistance to direct-acting antivirals in sub-Saharan Africa a threat to HCV elimination? Recommendations for action

“…Prospective data from SSA have shown lower treatment success with sofosbuvir and ledipasvir, particularly in genotype 4 subtypes. 5 Although these subtypes may be considered "unusual" or "rare" in high-resource settings, this is not the case in large populations in SSA. Such subtypes actually predominate or, in some cases, represent the entirety of HCV infections in countries such as Ethiopia, the Democratic Republic of Congo, Cameroon, Uganda, and Rwanda.…”