J Antimicrob Chemother

BACKGROUND: Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection. OBJECTIVES: To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. METHODS: This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines. RESULTS: Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration. CONCLUSIONS: Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease

Outcomes of targeted treatment in immunocompromised patients with asymptomatic or mild COVID-19: a retrospective study

Abstract The aim of this study was to describe the outcomes of targeted COVID-19 treatments in immunocompromised patients with asymptomatic or mild COVID-19 during the period of expansion of the different Omicron subvariants in France. A retrospective monocentric observational study was performed. All immunocompromised patients aged 18 or more, with asymptomatic SARS-CoV-2 infection or mild COVID-19, and who had received a targeted treatment with sotrovimab, tixagevimab/cilgavimab, nirmatrelvir/ritonavir or remdesivir at the Bordeaux University Hospital from 1st January 2022 to 31st December 2022 were eligible. The primary outcomes of interest was defined as a composite of either (i) progression to moderate (WHO-Clinical Progression Scale at 4 or 5) or severe COVID-19 (WHO-CPS ≥ 6), or (ii) the occurrence of COVID-19-related death. The secondary outcomes of interest were the components of the primary outcome. Outcomes were collected until day 30 after targeted treatment administration or at discharge for patients still hospitalised in relation with COVID-19 at day 30. 223 immunocompromised patients received targeted treatment for asymptomatic SARS-CoV-2 infection or mild COVID-19: 114 received sotrovimab, 50 tixagevimab/cilgavimab, 49 nirmatrelvir/ritonavir, and 10 remdesivir. Among 223 treated patients, 10 (4.5%) progressed to moderate or severe disease: three patients (1.3%) progressed to moderate COVID-19 and 7 (3.1%) patients progressed to severe disease. Among them, 4 (1.8%) died of COVID-19. More than 95% of immunocompromised patients with asymptomatic SARS-CoV-2 infection or mild COVID-19 treated by targeted therapies during the Omicron subvariants era did not progress to moderate or severe disease