A simple, feasible, efficient and safe treatment strategy of sofosbuvir/velpatasvir for chronic HCV/HIV-1 coinfected patients regardless of HCV genotypes: a multicenter, open-label study in China.

Background: The direct-acting antiviral agents (DAAs) have revolutionized the treatment of Hepatitis C Virus (HCV) infection. However, a simple and feasible treatment strategy with high efficacy and safety for HCV in patients coinfected with Human Immunodeficiency Virus (HIV) remains an unmet medical need, especially in areas with limited health resource. This study aims to assess the efficacy and safety of 12 weeks of treatment with sofosbuvir and velpatasvir in patients with chronic HCV/HIV-1 coinfection. Methods: We conducted a multicenter, single-arm, open-label study in China, which involved chronic HCV/HIV-1 coinfected patients who are receiving an antiretroviral regimen of a combination tablet consisting of elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide, (EVG/c/FTC/TAF) once daily. Patients with liver cirrhosis or experienced to DAAs treatment were excluded. All patients received combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks regardless of HCV genotype. The primary efficacy endpoint was sustained virologic response, defined as HCV RNA <15 IU/mL at 12 weeks after completion of treatment (SVR12). The primary safety endpoint was the proportion of patients who prematurely discontinued treatment because of adverse events. Safety and efficacy data were analyzed with an intention-to-treat (ITT) population (last observation carried forward) and per-protocol (PP) population. This trial is registered on ChiCTR.org.cn with number being ChiCTR1800020246. Findings: Of the 243 patients enrolled, 78% were male, 9% had been previously treated for HCV with interferon, and none had pre-defined cirrhosis, although 8% had Fibrosis 4 score (FIB-4) >3.25. A total of 233 patients completed 12-week post-treatment follow-up. Overall, 227/233 patients (97%) achieved SVR12: 100% (63/63) in those with HCV genotype 1, 67% (2/3) in those with genotype 2, 95% (84/88) in those with genotype 3, 99% (78/79) in those with genotype 6. Rates of SVR12 were lower among those with baseline FIB-4 >3.25 than those without (78% [14/18] vs. 99% [211/212], P < 0.001). HIV-1 suppression was not compromised. The most common adverse events were upper respiratory tract infection (5%), cough (3%), abnormal renal function (2%), abnormal liver function (2%), constipation (2%), urinary tract infection (2%) and sleep disorders (2%). No participant discontinued treatment because of adverse events or death. Interpretation: Twelve weeks of treatment with sofosbuvir/velpatasvir provide high rates of SVR and is well-tolerated in patients coinfected with HIV-1 and HCV regardless of HCV genotypes. Non-invasive liver fibrosis score may help to further distinguish patients at greater likelihood of a suboptimal response. Funding: The 13th Five Year Plan of the Ministry of Science and Technology of China for the prevention and treatment of major infectious diseases such as AIDS and viral hepatitis, the National Key Research and Development Program of China, Medical Key Discipline Program of Guangzhou-Viral Infectious Diseases (2021-2023), Basic research program on people's Livelihood Science and technology of Guangzhou, and National Natural Science Foundation of China.