MATERIALS AND METHODS: Between 16-April-2020 to 30-April- 2020, patients with suspected or confirmed for COVID-19 indicated for in-patient treatment with hydroxychloroquine with or without lopinavir-ritonavir to the Sarawak General Hospital were monitored with KardiaMobile smartphone electrocardiogram (AliveCor®, Mountain View, CA) or standard 12-lead electrocardiogram. The baseline and serial QTc intervals were monitored till the last dose of medications or until the normalization of the QTc interval.
RESULTS: Thirty patients were treated with hydroxychloroquine, and 20 (66.7%) patients received a combination of hydroxychloroquine and lopinavir-ritonavir therapy. The maximum QTc interval was significantly prolonged compared to baseline (434.6±28.2msec vs. 458.6±47.1msec, p=0.001). The maximum QTc interval (456.1±45.7msec vs. 464.6±45.2msec, p=0.635) and the delta QTc (32.6±38.5msec vs. 26.3±35.8msec, p=0.658) were not significantly different between patients on hydroxychloroquine or a combination of hydroxychloroquine and lopinavir-ritonavir. Five (16.7%) patients had QTc of 500msec or more. Four (13.3%) patients required discontinuation of hydroxychloroquine and 3 (10.0%) patients required discontinuation of lopinavirritonavir due to QTc prolongation. However, no torsade de pointes was observed.
CONCLUSIONS: QTc monitoring using smartphone electrocardiogram was feasible in COVID-19 patients treated with hydroxychloroquine with or without lopinavir-ritonavir. The usage of hydroxychloroquine and lopinavir-ritonavir resulted in QTc prolongation, but no torsade de pointes or arrhythmogenic death was observed.
METHODS: Using empirical data from Hartford, Connecticut, we deployed a stochastic block model to simulate an injection network of 1574 PWID. We used a susceptible-infected model for HCV and human immunodeficiency virus to evaluate the effectiveness of several HCV TasP strategies, including in combination with OAT and SSP scale-up, over 20 years.
RESULTS: At the highest HCV prevalence (75%), when OAT coverage is increased from 10% to 40%, combined with HCV treatment of 10% per year and SSP scale up to 40%, the time to achieve microelimination is reduced from 18.4 to 11.6 years. At the current HCV prevalence (60%), HCV TasP strategies as low as 10% coverage per year may achieve HCV microelimination within 10 years, with minimal impact from additional OAT scale-up. Strategies based on mass initial HCV treatment (50 per 100 PWID the first year followed by 5 per 100 PWID thereafter) were most effective in settings with HCV prevalence of 60% or lower.
CONCLUSIONS: Scale-up of HCV TasP is the most effective strategy for microelimination of HCV. OAT scale-up, however, scale-up may be synergistic toward achieving microelimination goals when HCV prevalence exceeds 60% and when HCV treatment coverage is 10 per 100 PWID per year or lower.
METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.
RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.
CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).