Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Prevalence of resistance-associated substitutions to NS3, NS5A and NS5B inhibitors at DAA-failure in hepatitis C virus in Italy from 2015 to 2019.

Despite the high efficacy of direct-acting antivirals (DAAs), the selection of resistance-associated substitutions (RASs) after virological failure of hepatitis C virus (HCV) DAAs can impair the cure of chronic HCV. The aim of the study was to characterize RASs after virological failure of DAAs in Italy over the years. Within the Italian network VIRONET-C, the change in prevalence of NS3/4A-NS5A-NS5B RASs was retrospectively evaluated in patients who failed a DAA regimen over the years 2015-2019. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols and the geno2pheno system was used to define HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend. Predictors of RASs at failure were analysed by logistic regression. Among 468 HCV-infected patients, HCV genotype 1 was the most prevalent (1b in 154, 33% and 1a in 109, 23%). DAA regimens were: ledipasvir (LDV)/sofosbuvir (SOF) in 131 patients (28%), daclatasvir (DCV)/SOF in 109 (23%), ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) in 89 (19%), elbasvir (EBR)/grazoprevir (GRZ) in 52 (10.5%), velpatasvir (VEL)/SOF in 53 (11%), glecaprevir (GLE)/pibrentasvir (PIB) in 27 (6%) and ombitasvir/paritaprevir/ritonavir (2D) in 7 (1.5%); ribavirin was administered in 133 (28%). The NS5A fasta sequence was available for all patients, NS5B and NS3/4A both for 93%. The prevalence of NS5A and NS3/4A RASs significantly declined from 2015 to 2019; NS5B RAS remained stable. Independent predictors of any RASs included older age and genotype 1a (vs G2 and vs G4). Notably, at least partial susceptibility to all the agents included in the GLE/PIB and VEL/SOF/Voxilaprevir (VOX) combinations was predicted in >95% of cases. As RASs remain common at the failure of DAAs, their identification could play a crucial role in optimizing re-treatment strategies. In Italy RAS prevalence has been decreasing over the years and susceptibility to the latest developed drug combinations is maintained in most cases.

Long-Term Serological Response to 13-Valent Pneumococcal Conjugate Vaccine Versus 23-Valent Polysaccharide Vaccine in HIV-Infected Adults.

INTRODUCTION: Long-term comparative immunologic response to 13-valent pneumococcal conjugate vaccine (PCV13) versus 23-valent polysaccharide vaccine (PPV23) among HIV-infected adults has not yet been investigated. METHODS: In this prospective pilot study, we quantified in HIV-positive adults serotype-specific IgG concentrations of the 12 pneumococcal serotypes shared by both vaccines 5 years after vaccination with two doses of PCV13 8 weeks apart (group 1) or one dose of PPV23 (group 2) and compared them with those assessed prior to vaccination (BL) and after 1 year (T1). Comparison of immunogenicity was based on geometric mean concentration (GMC), proportion of individuals with ≥ twofold increase from BL in specific antibody concentration against ≥ 2 serotypes and percentage of individuals with serotype-specific IgG ≥ 0.35 µg/ml, ≥ 1 µg/ml and ≥ individual serotype-specific correlates of protection. RESULTS: We included 91 subjects (median CD4+ 650 cells/µl, > 90% with HIV-RNA < 50 copies/ml); patients in groups 1 (n = 42) and 2 (n = 49) were homogeneous for the main characteristics. GMCs were significantly higher in the PCV13 group than in the PPV23 group for serotype 19F (p = 0.003). Both vaccines revealed higher significant GMCs to most serotypes compared with BL, i.e., eight in group 1 vs. seven in group 2. With respect to T1, GMCs decreased significantly in the PCV13 group for eight vs. ten serotypes in the PPV23 group. More participants in the PCV13 group had ≥ 2 increase from BL in antibody levels to ≥ 2 serotypes compared with the PPV23 group (78.6% vs. 59.2%, p = 0.042). Overall, the percentage of subjects with serotype-specific IgG ≥ 0.35 µg/ml, ≥ 1 µg/ml and ≥ individual serotype-specific correlates of protection was similar between groups. CONCLUSION: In this study with HIV-positive adults with a favorable viro-immunologic profile, both vaccines were shown to achieve a long-term durable serologic response. We found minor differences in immunogenicity between the two vaccines, which favored PCV13 over PPV23 5 years after immunization. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02123433.

Use of miltefosine in a patient with mucosal leishmaniasis and HIV-coinfection: a challenge in long-term management.

The management of mucosal leishmaniasis in immunocompromised patients is not standardized and limited data are available on the use of miltefosine for treatment and secondary prophylaxis. We describe a case of mucosal leishmaniasis in an HIV-coinfected patient treated with miltefosine due to a severe allergic reaction to liposomal amphotericin B.