Background The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov , NCT04315948 . Findings Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporea...

C, Mentre F, on behalf of the DisCoVeRy study group, An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with Clinical Microbiology and Infection,

BackgroundThe purpose of this study was to assess the short- and long-term outcomes of HIV-infected patients admitted to intensive care units (ICU) according to immunovirological status at admission and highly active antiretroviral therapy (HAART) use in ICU.MethodsRetrospective study of 98 HIV-infected patients hospitalized between 1997 and 2008 in two medical ICU in Montpellier, France. The primary outcome was mortality in ICU. The secondary end point was probability of survival in the year following ICU admission.ResultsEighty-two (83.6%) admissions in ICU were related to HIV infection and 45% of patients had received HAART before admission. Sixty-two patients (63.3%) were discharged from ICU, and 34 (34.7%) were alive at 1 year. Plasma HIV RNA viral load (VL) and CD4+ cell count separately were not associated with outcome. Independent predictors of ICU mortality were the use of vasopressive agents (odds ratio (OR), 3.779; 95% confidence interval (CI), 1.11–12.861; p = 0.0334) and SAPS II score (OR, 1.04; 95% CI, 1.003-1.077; p = 0.0319), whereas introducing or continuing HAART in ICU was protective (OR, 0.278; 95% CI, 0.082-0.939; p = 0.0393). Factors independently associated with 1-year mortality were immunovirological status with high VL (>3 log10/ml) and low CD4 (<200/mm3; hazard ratio (HR), 5.19; 95% CI, 1.328-20.279; p = 0.0179) or low VL (<3 log10/ml) and low CD4 (HR, 4.714; 95% CI, 1.178-18.867; p = 0.0284) vs. high CD4 and low VL, coinfection with C hepatitis virus (HR, 3.268; 95% CI, 1.29-8.278; p = 0.0125), the use of vasopressive agents (HR, 3.68; 95% CI, 1.394-9.716; p = 0.0085), and SAPS II score (HR, 1.09; 95% CI, 1.057-1.124; p <0.0001). Introducing HAART in a patient with no HAART at admission was associated with a better long-term outcome (HR, 0.166; 95% CI, 0.043-0.642; p = 0.0093).ConclusionsIn a population of HIV-infected patients admitted to ICU, short- and long-term outcomes are related to acute illness severity and immunovirological status at admission. Complementary studies are necessary to identify HIV-infected patients who benefit from HAART use in ICU according to immunovirological status and the reasons of ICU admission.

Purpose of Review Lung cancer is emerging as a leading cause of death in HIV infected persons. This review will discuss the latest scientific evidence regarding the mechanisms driving lung cancer risk in HIV infection, the clinical presentation of lung cancer in HIV infected persons, and recent data regarding the outcomes, treatment and prevention of lung cancer in this group. Recent Findings Increased risk of lung cancer in HIV infected persons is primarily due to higher smoking rates, but emerging evidence also implicates immunosuppression and inflammatory processes. Lung cancer outcomes may be worse in HIV infected persons in the anti-retroviral era but this may stem, in part, from treatment disparities. Early detection of lung cancer using chest computed tomography (CT) is being increasingly adopted for smokers in the general population and recent studies suggest it may be safe and efficacious in HIV infected smokers. Summary Lung cancer is an important complication associated with chronic HIV infection. It is associated with unique HIV-related causal mechanisms, and may be associated with worse outcomes in some HIV infected persons. Smoking cessation and early cancer detection with chest CT are likely to benefit HIV infected smokers.