Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies.

Objectives: The phase 2 MANTA and MANTA-RAy studies aimed to determine if the oral Janus kinase 1 preferential inhibitor filgotinib affects semen parameters and sex hormones in men with inflammatory diseases.

Methods: MANTA (NCT03201445) and MANTA-RAy (NCT03926195) included men (21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases (rheumatoid arthritis, spondyloarthritis or psoriatic arthritis), respectively. Eligible participants had semen parameters in the normal range per the WHO definition.

Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients.

Background & Aims: Sofosbuvir, an NS5B inhibitor, combined with velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1-6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1-4 HCV infection after liver transplant.

Methods: Patients received SOF/VEL 400/100 mg daily for 12 weeks.

Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients Treated with Ledipasvir / Sofosbuvir Plus Ribavirin Pretransplant.

Introduction: Recurrence of HCV infection in patients with chronic hepatitis C virus (HCV) at the time of liver transplantation is nearly universal and reduces the likelihood of graft and patient survival.

Materials And Methods: We evaluated outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all patients, HCV RNA was < 15 IU/mL prior to transplant.

Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial.

Background: Treatment options are limited for patients infected by hepatitis C virus (HCV) with advanced liver disease. We assessed the safety and efficacy of ledipasvir, sofosbuvir, and ribavirin in patients with HCV genotype 1 or 4 and advanced liver disease.

Methods: We did an open-label study at 34 sites in Europe, Canada, Australia, and New Zealand.

Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease.

Background & Aims: There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease.

Methods: In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation.

A randomized, open-label study of the safety and efficacy of switching stavudine or zidovudine to tenofovir disoproxil fumarate in HIV-1-infected children with virologic suppression.

Background: The safety and efficacy of tenofovir disoproxil fumarate (TDF) in HIV-1-infected children have not been evaluated in a randomized controlled trial.

Methods: Subjects (2 to <16 years) on a stavudine (d4T) or zidovudine (ZDV) containing regimen with HIV-1 RNA <400 copies/mL were randomized to either switch d4T or ZDV to TDF or continue d4T or ZDV. The primary endpoint was the proportion of subjects with HIV-1 RNA < 400 copies/mL at Week 48 with a prespecified noninferiority margin of 15%.

Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation.

Background & Aims: Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection.

Methods: In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation.

Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study.

Background & Aims: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward.

Sofosbuvir for previously untreated chronic hepatitis C infection.

Background: In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection.

Methods: We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4).

A randomized study of tenofovir disoproxil fumarate in treatment-experienced HIV-1 infected adolescents.

Background: There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents.

Methods: A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to <18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean, 216.

The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C.

Unlabelled: Tegobuvir (GS-9190), a non-nucleoside nonstructural protein (NS)5B polymerase inhibitor, and GS-9256, an NS3 serine protease inhibitor, individually have activity against hepatitis C virus (HCV) genotype 1. The antiviral activity of tegobuvir and GS-9256 as oral combination therapy, or together with ribavirin (RBV) or pegylated interferon (Peg-IFN) alpha-2a and RBV, was assessed in a phase II, randomized, open-label trial. Treatment-naïve patients with genotype 1 HCV were assigned 28 days of tegobuvir 40 mg twice-daily (BID) and GS-9256 75 mg BID (n = 16), tegobuvir and GS-9256 plus RBV 1,000-1,200 mg daily (n = 15), or tegobuvir and GS-9256 plus Peg-IFN alpha-2a (180 μg once-weekly)/RBV (n = 15).

Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial.

Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving ≥3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central α-2 agonist guanfacine.

Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B.

Unlabelled: Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES).

Pooled analysis of amino acid changes in the HBV polymerase in patients from four major adefovir dipivoxil clinical trials.

Background/aims: The rtA181V and rtN236T mutations have been associated with resistance to adefovir dipivoxil (ADV). Recent reports have proposed other ADV resistance (ADV-R) mutations. The aims of this study were to confirm the role of rtA181V and rtN236T in clinical resistance to ADV and to screen for other potential ADV-R mutations.

Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B: final long-term results.

Wait-listed (n = 226) or post-liver transplantation (n = 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (<1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively.

Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years.

Background & Aims: Treatment with adefovir dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of adefovir dipivoxil treatment for up to 240 weeks.

Methods: HBeAg-negative patients were treated double blind with placebo or adefovir dipivoxil 10 mg once daily for 48 weeks, followed by adefovir dipivoxil from week 49 to 96.

Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B.

Background: Treatment with adefovir dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy.

Methods: One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks (ratio, 2:1).