Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401–4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

The genotypes of 149 HCV strains from St. Petersburg were determined by limited sequencing and phylogenetic analysis within the NS5B region. One hundred two strains derived from patients that attended infectious disease clinics, of whom 48 admitted injecting drug use, and 47 derived from dialysis patients. Subtype 3a was predominant in the patients from infectious disease clinics, both in patients that admitted injecting drug use (56%) and in those with unknown source of infection (46%). However, 89% of the strains from dialysis patients belonged to subtype 1b. Eleven of twelve characterised strains from recent cases of hepatitis C at these units were at phylogenetic analysis shown to be related to strains already circulating there, demonstrating that within the dialysis units nosocomial transmission is the most important route of HCV infection. The predominance of subtype 1b strains in dialysis patients indicates that these strains have been circulating for a long time in dialysis units. The predominance of subtype 3a also among patients who did not admit drug use and that their strains were intermixed with the strains from injecting drug users in the phylogenetic analysis shows that the increase in injecting drug use is the major factor that explains the recent spread of HCV in the St. Petersburg population. This supports the concept that injecting drug use remains the major route for HCV infection in developed countries and that the control of drug abuse is the most important measure to prevent its spread.

The prevalence of hepatitis C virus (HCV) infection in Asian countries is high. This study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from Asia‐Pacific countries and Russia. In this phase 3, randomized, placebo‐controlled, double‐blind study, treatment‐naive participants with HCV genotype (GT) 1, 4, or 6 infection were randomized to EBR 50 mg/GZR 100 mg (immediate‐treatment group [ITG]) or placebo (deferred‐treatment group [DTG]) once daily for 12 weeks (Protocol PN‐5172‐067, NCT02251990). The primary efficacy variable was a nonrandomized comparison of sustained virologic response at 12 weeks after the end of therapy (SVR12) for the ITG with a historical control. The primary safety outcome was a randomized comparison between the ITG and DTG. Three hundred thirty‐seven participants were randomized to the ITG (n = 251) or DTG (n = 86); 199 (59.2%) participants were Asian, and 250 (74.4%) had HCV GT1b infection. Overall, 232/250 (92.8%) participants in the ITG achieved SVR12 (97.5% confidence interval, 89.1, 96.5). Of the 18 participants who failed to attain SVR12, 1 was lost to follow‐up and 17 had virologic failure, 13 of whom had HCV GT6 infection. The incidence of adverse events was similar between participants receiving EBR/GZR and placebo (50.8% versus 51.2%; difference, −0.3%; 95% confidence interval, −12.3, 11.9). Conclusion: EBR/GZR for 12 weeks provides an effective and well‐tolerated regimen for chronic HCV GT1 infection in treatment‐naive people from Asia‐Pacific countries and Russia, particularly for the large population with GT1b infection. EBR/GZR is not recommended for the treatment of individuals with HCV GT6 infection. (Hepatology Communications 2018;2:595‐606)

Background and Aim: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). Methods: C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferredtreatment group. Results: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediatetreatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). Conclusions: Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia. fees from AbbVie, Bristol-

Sofosbuvir plus ribavirin for 16 or 24 weeks was associated with a high SVR rate in patients with HCV genotype-3. Among HCV genotype-1b patients, the presence of the L159F variant at baseline was associated with a lower SVR rate in those treated for 16 weeks but not in those treated for 24 weeks. Sofosbuvir plus ribavirin was safe and well tolerated regardless of treatment duration. Clinicaltrials.gov number NCT01896193.