Explore the vast range of titles available.

In patients with HCV genotypes 2 and 3, sofosbuvir plus ribavirin was administered for 12 weeks in patients with genotype 2 and for 24 weeks in those with genotype 3. Rates of sustained virologic response were 93% in patients with genotype 2 and 85% in those with genotype 3. Of the six main genotypes of the hepatitis C virus (HCV), genotypes 2 and 3 account for approximately 30% of chronic infections worldwide. 1 Although these two genotypes have historically been grouped together in treatment guidelines and clinical trials, 2 , 3 accumulating evidence suggests that there are important clinical differences between them. 1 , 4 , 5 HCV genotype 3 infection is associated with a higher incidence of hepatic steatosis, more rapid progression of fibrosis, and possibly a greater risk of hepatocellular carcinoma than is HCV genotype 2 infection. 6 Moreover, patients with HCV genotype 3 infection are less responsive to peginterferon-based treatment than are patients . . .

Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system). Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug. In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis. Gilead Sciences.

In two studies of sofosbuvir for previously untreated HCV infection, patients with genotype 1, 4, 5, or 6 had a 90% rate of sustained virologic response in a single-group study. In a study of sofosbuvir–ribavirin versus peginterferon–ribavirin for patients with genotype 2 or 3, the response rate was 67% in each group. As many as 170 million persons are chronically infected with the hepatitis C virus (HCV) worldwide, and more than 350,000 die annually from liver disease caused by HCV. 1 , 2 Estimates of the number of persons in the United States who have chronic HCV infection range from 2.7 million to 5.2 million. 3 , 4 For previously untreated cases of HCV genotype 1 infection (representing more than 70% of all cases of chronic HCV infection in the United States), the current standard of care is 12 to 32 weeks of an oral protease inhibitor combined with 24 to 48 weeks of peginterferon alfa-2a . . .

In two randomized trials, the oral nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 12 or 16 weeks was effective in patients with chronic HCV genotype 2 or 3 infection for whom interferon therapy either was not an option or had failed. When studied in clinical trials, the current standard-of-care therapy for patients with hepatitis C virus (HCV) genotype 2 or 3 infection — pegylated interferon in combination with ribavirin for 24 weeks — resulted in a sustained virologic response in 70 to 85% of patients who had not received prior treatment and in 55 to 60% of those who had received treatment. 1 – 4 However, a substantial proportion of patients with HCV infection remain untreated owing to absolute or relative contraindications to interferon therapy, such as hepatic decompensation, autoimmune disease, and psychiatric illness. 5 In addition, interferon causes a range of constitutional symptoms . . .

Background Long-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks). Aim We assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients. Methods Patients who completed 1 year (48 weeks) of randomized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years (384 weeks). Results Of 641 patients initially randomized, 585 (91.3 %) entered the open-label phase; 437/585 (74.7 %) remained on study at year 7. For patients on treatment at year 7, 99.3 % maintained viral suppression (HBV DNA < 69 IU/mL), 80.0 % achieved serum alanine aminotransferase normalization, and in HBeAg-positive patients, 84/154 (54.5 %) and 25/154 (11.8 %) achieved HBeAg and HBsAg loss, respectively. One/375 (0.3 %) HBeAg-negative patients achieved HBsAg loss. No resistance to TDF was detected through 7 years. During the open-label phase, grade 3/4 drug-related adverse events were uncommon (1.0 %); ten (1.7 %) patients had elevation of serum creatinine ≥0.5 mg/dL above baseline. No significant change in bone mineral density was observed from year 4 to year 7 (week 192 to week 336). Conclusions Long-term TDF treatment was associated with sustained virologic, biochemical, and serologic responses, without resistance. TDF treatment was well tolerated, with a low incidence of renal and bone events. These data confirm the safety and efficacy of long-term TDF for CHB.

In this study in patients with HCV genotype 1 infection and prior treatment failure, those assigned to 12 weeks or 24 weeks of treatment with ledipasvir and sofosbuvir, with or without ribavirin, had high rates of sustained response (94 to 99% in all groups). Among the estimated 170 million people in the world who have chronic hepatitis C virus (HCV) infection, approximately 60% have the genotype 1 strain of the virus. 1 The treatment of patients infected with HCV genotype 1 is evolving rapidly. 2 – 6 At the end of 2013, the Food and Drug Administration (FDA) approved two new direct-acting antiviral agents for the treatment of HCV infection: the nucleotide polymerase inhibitor sofosbuvir (Gilead Sciences) and the protease inhibitor simeprevir (Janssen Therapeutics). 7 , 8 Among the regimens that have been approved by the FDA for patients with HCV genotype 1 infection who have not had a . . .

In previously untreated patients with HCV genotype 1 infection without cirrhosis, the rate of sustained virologic response was 94% with 8 weeks of ledipasvir–sofosbuvir, 93% with 8 weeks of ledipasvir–sofosbuvir plus ribavirin, and 95% with 12 weeks of ledipasvir–sofosbuvir. More than 3 million people in the United States are chronically infected with the hepatitis C virus (HCV). 1 , 2 Although the number of new infections has been declining for decades, HCV-related morbidity and mortality are projected to continue rising for another 20 years. 3 One half to three quarters of persons currently infected with HCV have not received a diagnosis and are untreated; many will have progression to decompensated cirrhosis, hepatocellular carcinoma, and other liver complications. 3 , 4 Early diagnosis and treatment are essential to improve long-term health outcomes in this population. New guidelines from the Centers for Disease Control and Prevention . . .

•GS-4774 is being developed as a therapeutic vaccine for chronic HBV infection.•GS-4774 consists of yeast cells that express well-conserved regions of HBV proteins.•GS-4774 was safe and well-tolerated in healthy subjects at all doses evaluated.•GS-4774 led to HBV-specific immune responses after weekly and monthly immunization.•GS-4774 is being tested in patients with chronic HBV infection. GS-4774 is a recombinant, heat-killed, yeast-based immunotherapy engineered to express hepatitis B virus (HBV)-specific antigens. GS-4774 is being developed as a therapeutic vaccine for chronic HBV infection. The aim of this study was to assess the safety, tolerability and immunogenicity of GS-4774 in healthy subjects. This was a randomized, open-label, dose-ascending study. Subjects were allocated to one of three dose groups (n=20 per group) to receive 10, 40 or 80 yeast units (YU; 1YU=107 yeast) of GS-4774 in two immunization regimens (five subcutaneous injections at weekly intervals with one monthly booster or three subcutaneous injections at monthly intervals). T-cell-mediated responses were determined by interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay and lymphocyte-proliferation assay (LPA). Adverse events were reported by 39 of 60 (65%) subjects; all were mild or moderate and none was serious. Adverse events occurred most frequently in the highest dose group, 80YU, and the number of individual events was higher after weekly immunization than monthly. The most common adverse events were injection-site reactions. Most (88%) subjects responded to GS-4774 by at least one of the T-cell assays. Following immunization with GS-4774, IFN-γ-producing T-cells specific for HBV antigens were detectable in 30 (51%) subjects. The ELISpot response was observed at all doses, with the highest frequency of responders occurring at the highest dose (10YU: 45%; 40YU: 35%; 80YU: 74%). Proliferative responses to HBV recombinant antigens were observed in 90% subjects; responses were mainly independent of GS-4774 dose and immunization regimen. GS-4774 was safe and well-tolerated in healthy subjects with injection-site reactions being the most frequently reported adverse events. With both weekly and monthly regimens, GS-4774 provided HBV-specific immune responses at all doses evaluated. Further evaluation of GS-4774 is ongoing in patients with chronic HBV infection. Clinical trial registry: Clinicaltrials.gov (NCT01779505)

Demonstration of a new, effective therapy for human anthrax disease is quite challenging, given the rarity of clinical illness. In this study, a monoclonal antibody against the protective antigen of anthrax toxin was shown to be beneficial in two animal models of anthrax infection; the dose required to achieve similar benefit in humans was determined. A monoclonal antibody against the protective antigen of anthrax toxin was shown to be beneficial in two animal models of anthrax infection; the dose required to achieve similar benefit in humans was determined. Bacillus anthracis causes anthrax, a zoonotic infection affecting a wide range of mammalian species, and it can be transmitted from animals to humans. 1 The innate hardiness of B. anthracis endospores has allowed anthrax spores to be developed as “weapons-grade” material for biologic weapons. 2 The largest outbreak of inhalational anthrax occurred in 1979 in Sverdlovsk (in the former Soviet Union), 3 and the 2001 anthrax attacks were the first confirmed outbreak associated with intentional anthrax release in the United States. 4 , 5 Inhalational anthrax exposure rapidly progresses to bacteremia and toxemia, with mortality ranging from 45 to 80%. 1 , 2 , 5 Although several antibiotics . . .

Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection. We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1–4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678. Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77–91) in patients with genotype-1 HCV, 88% (69–98) in patients with genotype-2 HCV, 89% (81–94) in patients with genotype-3 HCV, and 84% (66–95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67–99] and 91% [81–97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36–100] and 86% [73–94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse. Six (2%) patients discontinued treatment because of adverse events. The most common adverse events were fatigue, insomnia, asthenia, and headache. Four (1%) patients had serious adverse events regarded as related to study treatment. Additionally, four (1%) patients receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen. Sofosbuvir and ribavirin provided high rates of sustained virological response after 12 weeks of treatment in treatment-naive and treatment-experienced patients co-infected with HIV and HCV genotypes 1–4. The characteristics of this interferon-free combination regimen make sofosbuvir plus ribavirin a useful treatment option for this patient population. Gilead Sciences.