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OBJECTIVES: We designed a prospective cohort study to systematically study patients with severe acute respiratory infection (SARI) and improve hospital preparedness (SARI-PREP). The goal of this project is to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with SARI clinical outcomes and severity. METHODS: In collaboration with the Society of Critical Care Medicine Discovery Research Network and the National Emerging Special Pathogen Training and Education Center (NETEC), SARIPREP is an ongoing, prospective, observational, multi-center cohort study of hospitalized patients with respiratory viral infections. We collected patient demographics, signs, symptoms, and medications;microbiology, imaging, and other diagnostics;mechanical ventilation, hospital procedures, and other interventions;and clinical outcomes. Hospital leadership completed a weekly hospital stress survey. Respiratory, blood, and urine biospecimens were collected from patients on days 0, 3, 7-14 after study enrollment and at hospital discharge. MEASUREMENTS AND MAIN RESULTS: SARI-PREP enrollment began on April 4, 2020 and currently includes 674 patients. Here we report results from the first 400 patients: 216 are from the University of Washington Hospitals, Seattle WA, 142 from New York University, New York NY and 42 from University of Southern California, Los Angeles, CA. Almost all tested positive for SARS-CoV-2 infection (n=397), whereas 3 patients tested positive for an alternative viral pathogen. The mean (±SD) age of the patients was 57±16 years;72% were men, 62% were White, 14% were Asian, 12% were Black, and 31% were Hispanic. Most of the patients were admitted to the intensive care unit (96%). The median (interquartile range) hospital length of stay was 22 (9-46) days. Rates of invasive mechanical ventilation (72%) and renal replacement therapy (19%) were common and the rate of hospital mortality was 35%. CONCLUSIONS: Initial SARI-PREP analysis indicates enrollment of a diverse population of hospitalized patients primarily with SARSCoV-2 infection. The demographics and clinical outcomes of our cohort mirror other large critically ill cohorts of COVID-19 patients. Results of a concomitant, weekly, hospital stress assessment are reported separately.
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At the 2021 Conference on Retroviruses and Opportunistic Infections, there was a focus on progress toward hepatitis C virus (HCV) microelimination in geographic regions and targeted populations. HCV elimination is facilitated by well-tolerated, highly effective HCV treatment that requires essentially no on-treatment monitoring in most patients, as highlighted by the MINMON (Minimal Monitoring Study or A5360) study, and that should be increasingly available to children with new data supporting feasible treatment in younger patients. Challenges to HCV elimination include HCV reinfection via sexual exposure in men who have sex with men (MSM) and continued barriers to diagnosis and access to HCV treatment. Hepatitis B virus (HBV) suppression may take years in HIV/HBV-coinfected patients. This may have important consequences as the risk for hepatocellular carcinoma was associated in a dose-dependent manner with HBV viral load and was lowest in those with sustained undetectable HBV, highlighting the need for HBV DNA monitoring during therapy. Public health programs should prioritize improving hepatitis A and hepatitis B vaccination in at-risk populations, including people with HIV, as vaccinations rates for these preventable diseases continue to be suboptimal in many settings. Fatty liver disease, heavy alcohol use, antiretroviral therapy, and COVID-19 infection were also examined as drivers of hepatic disease in HIV infection.
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Background: To achieve global hepatitis C virus (HCV) elimination by 2030, 80% of the ∼71 million people with chronic HCV need to be treated, necessitating simplification of treatment delivery and associated laboratory monitoring without compromising efficacy or safety. The COVID-19 pandemic has further highlighted the need for innovative models that minimize face-toface contact. Methods: ACTG A5360 is a single-arm, open-label trial to evaluate safety and efficacy of a minimal monitoring (MINMON) approach to HCV therapy in treatment-naïve persons with no evidence of decompensated cirrhosis. All participants received a single-tablet, fixed-dose regimen of sofosbuvir/velpatasvir for 12 weeks. MINMON included: (1) no genotyping;(2) all tablets dispensed at entry;(3) no on-treatment visits/labs;and (4) two remote contacts at Weeks 4 (adherence assessment) and 22 (scheduling sustained virology response [SVR] visit). Unplanned visits for participant concerns (related/unrelated to an adverse event [AE]) were allowed. SVR is defined as HCV RNA <lower limit of quantification at least 22 weeks after treatment initiation (missing HCV RNA = failure). 95% confidence intervals (CI) for SVR used Wilson's Score. Results: 400 participants were enrolled from 10/2018-07/2019 at 38 sites in five countries across 4 continents;399 initiated treatment. Median age was 47 years, 138 (35%) were cisgender women, 22 (6%) self-identified across the transgender spectrum, and 166 (42%) were White. At entry, 34 (9%) had compensated cirrhosis (FIB-4 ≥3.25) and 166 (42%) had HIV co-infection. Remote contact was successful at Weeks 4 and 22 for 394 (99%) and 335 (84%) participants, respectively. HCV RNA for SVR was available for 396 participants. Overall, 95% (379/399) achieved SVR (95% CI: 92.4%, 96.7%);SVR by country, biological sex, gender identity, age, cirrhosis status, HIV co-infection status and injection drug use are presented in Figure. Fifteen (3.8%) participants had unplanned visits;3 were AE related and 6 were related to abnormalities during screening. Serious AE events through Week 24 visit were reported in 14 (3.5%) participants;none were treatment related or resulted in death. Conclusion: In a diverse, global patient population, the MINMON approach to HCV treatment delivery was safe and achieved SVR comparable to current standards. Wider adoption of this approach coupled with innovative casefinding strategies may facilitate HCV elimination while minimizing in-person appointments and resource use.