Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial.

BACKGROUND: We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. METHODS: This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates. RESULTS: Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68). CONCLUSIONS: Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses.

Overview of HIV treatment failure in Africa using the WHO Pharmacovigilance data.

OBJECTIVE: To characterise the factors associated with HIV treatment failure (HIVTF) from reported pharmacovigilance data in Africa. MATERIALS AND METHODS: This is an observational pharmacovigilance analysis of the safety data of HIVTF available in the WHO International Pharmacovigilance database 'VigiBase® '. We used the Standardised MedDRA Queries (SMQ) to identify all the terms corresponding to HIVTF. To identify all relevant molecules and classes of antiretroviral therapy, we used the anatomic, therapeutic, and chemical classification. We presented results as a percentage or an adjusted Reporting Odds Ratio (aROR) with a 95% confidence interval (95% CI). RESULTS: HIVTF was more reported in Africa compared with the rest of the world with 19.1% (18.1%-20.1%) corresponding to 1206 of all 6304 HIVTF reports. Among all the 37 WHO country members in Africa, South Africa was the main source of origin for these HIVTF reports with 86.8% (84.9%-88.7%). Compared to adults, children and adolescents were the most population groups affected by HIVTF, aROR = 2.7, (95% CI) 1.7-4.2 and aROR = 7.9, (95% CI) 4.5-13.9, respectively. CONCLUSION: South Africa was the leading country of the reporting of HIVTF in Africa. The proportion of HIVTF was higher in both HIV-infected children and adolescents than in adults. There is a need for the improvement of medical care for children and adolescents with HIV infection in Africa.

Statin therapy and low-density lipoprotein cholesterol reduction in HIV-infected individuals after acute coronary syndrome: Results from the PACS-HIV lipids substudy.

Knowledge about lipid interventions in secondary prevention in HIV-infected individuals is limited; studies are sparse. METHODS: A prospective observational multicenter study enrolled 282 patients on statin 1 month after first acute coronary syndrome (ACS) (95 HIV-infected individuals, 187 HIV-uninfected). Data on fasting lipids (total cholesterol [TC], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], non-HDL-C, triglycerides, TC/HDL-C ratio) were collected over 3 years. The evolution of lipid concentrations was analyzed using mixed-effects models. Achievement of National Cholesterol Education Program Adult Treatment Panel III lipid goals and prescribed statin intensity was assessed. RESULTS: Mean age of patients was 49.0 years, and 94% were men. Baseline lipids were similar in the 2 groups. Six months after first ACS, less low-density lipoprotein cholesterol reduction was observed in the HIV-infected GROUP (adjusted mean change -10.13; 95% CI -20.63 to 0.37; P=.06) than in the HIV-uninfected group (Adjusted mean change -38.51; 95% CI -46.00 to -31.04; P<.0001) Similar trends were observed for TC and non-HDL-C. After ACS, initial statin prescription for HIV-infected compared with HIV-uninfected individuals was more frequently a moderate-intensity statin (66% vs 45%) and less frequently a high-intensity statin (15% vs 45%). Over 3 years of follow-up, the proportion of HIV-infected patients receiving high-intensity statin remained persistently lower than the proportion observed in the HIV-uninfected group. CONCLUSIONS: In this observational study, HIV-infected individuals after first ACS exhibited worse lipid profiles than controls particularly during the first 6 months while receiving less potent statins. Appropriate statin intensity should be prescribed in HIV-infected individuals with awareness of potential drug-drug interactions.