Hepatitis C virus (HCV) infection is one of the main causes of liver disease worldwide. Its treatment is currently based on the combination of peg-interferon, ribavirin, and, for patients with genotype 1, a protease inhibitor (telaprevir or boceprevir). However, interferon-based combinations are not effective in all patients. Moreover, they are contraindicated in patients who cannot receive interferon (e.g. those with decompensated cirrhosis), and are frequently associated with adverse events. Consequently, there is a need to develop new drugs to treat HCV infection. This review focuses on preclinical and clinical data regarding sofosbuvir (GS-7977), a uridine nucleotide analogue inhibitor of HCV NS5 B polymerase that is effective against HCV genotypes 1,2, 3,4 and 6. Thanks to its excellent pharmacokinetic profile, sofosbuvir can be administered in an oral single daily dose. In vitro it exerts a potent antiviral effect against HCV. Clinical data show that combined with peg-interferon and ribavirin for 12 weeks it yields SVR of about 90% in subjects with HCV genotype 1 and about 100% in patients with HCV genotype 2 or 3. Moreover, sofosbuvir and ribavirin administered for 12 weeks yield similar high SVR rate (84% for genotype 1 and 100% for genotype 2/3 patients) as well as sofosbuvir and daclatasvir (an inhibitor of NS5A) which produce SVR rate of about 100% regardless of genotype or of ribavirin employment. Safety and tolerability of sofosbuvir appear to be excellent. In conclusion, sofosbuvir especially in interferon-free combinations represents a very promising option in the treatment of chronic hepatitis C.

Molnupiravir and nirmatrelvir were the first available oral antivirals (OAs) active against SARS-CoV-2. Trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy in order to provide real-life data on the efficacy and safety of OAs during the omicron surge of the COVID-19 pandemic. Among 257 patients, 56.8% received molnupiravir, while 43.2% received nirmatrelvir/ritonavir. Patients in the molnupiravir group were older, had a lower body mass index, and had a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir. Three hospitalizations were recorded in the molnupiravir (2.1%) group and one in the nirmatrelvir/ritonavir (0.9%) group. One patient treated with molnupiravir died. The median time to negativity was 8 days in the nirmatrelvir/ritonavir group vs. 10 days in the molnupiravir group, p < 0.01. We recorded 37 ADRs (mainly dysgeusia, diarrhea, and nausea) in 31 individuals (12.1%). Only two patients (0.8%) treated with molnupiravir terminated treatment due to ADRs. In conclusion, in a population of mostly vaccinated patients treated with OAs, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were lower than those reported in pivotal trials.

(2015). The discovery of sofosbuvir: a revolution for therapy of chronic hepatitis C. Expert Opinion on Drug Discovery: Vol. 10, No. 12, pp. 1363-1377. doi: 10.1517/17460441.2015.1094051

Introduction: Alemtuzumab is a monoclonal anti CD-52 antibody recently approved for use in relapsing-remitting multiple sclerosis(MS). Given that the targeted antigen is primarily expressed on B and T lymphocytes, the administration of this biological drug is associated with rapid but protracted peripheral lymphopenia. Areas covered: The impact on infective risk of this immune impairment is still to be fully understood. In this review, we attempt to summarize all the available literature concerning opportunistic infections occurring in patients with MS receiving alemtuzumab. Infective adverse events were observed in more than 70% of patients in phase 2/3 RCTs, mainly of mild-to-moderate severity. Nevertheless, several post-marketing reports documented cases of serious, rare, and unexpected infections. Expert Opinion: Predictive risk factors and prognostic features of opportunistic infections in this setting still need to be exactly assessed. At present, the only recommended preventive measures consist in anti-herpetic prophylaxis, Listeria-free diet, Tuberculosis prophylaxis and annual Papillomavirus screening. Given the non-negligible risk of unpredicted infective events, we advise physicians to take into account patients’ history of infectious diseases and vaccine status and to consider supplementary prophylactic strategies, including screening for Toxoplasma gondii and viral hepatitis serostatus as well as pre-emptive approaches to avert CMV reactivation and Pneumocystosis.