DAA developers face foreseeable challenges in the years to come. Therapeutic gaps for individuals with complicating conditioned such as chronic kidney disease and cirrhosis will need to be bridged. Shorter therapies with milder side effects would yield greater adherence, and the ever present spectre of drug resistance is looming. The highly adaptive HCV has evolved into a number of different genomes that all need to be adequately treated, preferably with pan-genotypic regimens.
Some of these challenges already have possible solutions in sight. The protease inhibitor ABT-493 and the next-generation NS5A inhibitor ABT-530 are considered active against all HCV genotypes, including the hard to treat genotype 3. In vitro, ABT-530 showed potency against the resistance associated variants which are immune to the first generations of NS5A inhibitors, including ledipasvir, daclatasvir and ombitasvir. Because this drug combination has the additional quality of being hepatically cleared, it holds the promise that patients with chronic kidney disease and HCV could receive a safe, non-sofosbuvir-based treatment in the near future.
At least three drug combinations for the treatment of HCV are in the pipeline to be approved in 2016-2017: Sofosbuvir in combination with velpatasvir, ABT-493 in combination with ABT-530, and grazoprevir in combination with elbasvir, of which velpatasvir, ABT-530 and elbasvir are NS5A inhibitors.