Background SARS‐CoV‐2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two‐step furin‐mediated entry mechanism. Aprotinin is a broad‐spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti‐inflammatory properties for inhibiting the innate immunity contact system. Methods This was a multicentre, double‐blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID‐19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30‐day follow‐up period. Treatment was given for 11 days or till discharge. Results With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182–4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin‐treated group required less oxygen therapy and had no adverse reactions or side effects. Conclusion Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID‐19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.

Background: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce. Objective: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort. Methods This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy. Results: We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA <50 copies/mL in the OT, mITT, and ITT groups were 94%, 80%, and 62%, respectively, after 12 months of BIC/FTC/TAF treatment. Rates of TE PLWH with HIV-RNA <50 copies/mL were 91%, 88%, and 75% at month 12. The multivariate analysis revealed that neither age, sex, CD4 cell count <200 cells/μL, or viral load >100 000 copies/mL were associated with therapeutic failure. Conclusion and relevance: Our real-life data showed that BIC/FTC/TAF is effective and safe for use in the treatment of both TN and TE patients in clinical practice.

How to cite this article: Redondo-Calvo FJ, Padín JF, Martínez-Alarcón J, et al. Inhaled aprotinin reduces viral load in mild-to-moderate inpatients with SARS-CoV-2 infection.