Barnaby FlowerLeanne McCabeChau Le NgocHung Le ManhPhuong Le ThanhThuan Dang TrongThu Vo ThiHang Vu Thi KimThanh Nguyen TatDao Phan Thi HongAn Nguyen Thi ChauTan Dinh ThiNga Tran Thi TuyetJoel TarningCherry KingsleyEvelyne KestelynSarah L. PettGuy ThwaitesVinh Chau Nguyen VanDavid SmithEleanor BarnesM. Azim AnsariHugo TurnerMotiur RahmanAnn Sarah WalkerJeremy DayGraham S. CookeOxford University Clinical Research UnitUniversity of OxfordUniversity College London Hospitals NHS Foundation TrustUniversity College LondonImperial College Faculty of MedicineImperial College LondonMahidol University2022-08-042022-08-042021-07-01Open Forum Infectious Diseases. Vol.8, No.7 (2021)232889572-s2.0-85112511379https://repository.li.mahidol.ac.th/handle/20.500.14594/78053Background: Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis. Methods: In this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/mL at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/mL received 24 weeks. Primary endpoint was sustained virological response (SVR). Results: Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline. Conclusions: Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.Mahidol UniversityMedicineArticleSCOPUS10.1093/ofid/ofab267