Amy Ackerberg-Hastings
John and Eliza Ware Rotch Farrar: A dual-career marriage in sickness and in health-but mostly sickness
Endeavour
effective antiviral drugs prevent hospitalisation death covid19 antiviral efficacy efficiently assessed vivo measuring rates sarscov2 clearance estimated serial viral genome densities quantitated nasopharyngeal oropharyngeal swab eluates conducted individual patient data metaanalysis unblinded arms platcov platform trial characterise changes viral clearance kinetics infer optimal design interpretation antiviral pharmacometric evaluations serial viral density data analysed symptomatic previously healthy adult patients within 4 days symptom onset enrolled large multicentre randomised adaptive pharmacodynamic platform trial platcov comparing antiviral interventions sarscov2 viral clearance rates 1 week estimated hierarchical bayesian linear model bsplines used characterise temporal changes enrolment viral densities clearance rates bootstrap resampling used assess optimal duration followup pharmacometric assessment optimal defined maximising expected z score comparing effective antivirals treatment platcov registered clinicaltrialsgov nct05041907 sept 29 2021 oct 20 2023 1262 patients randomly assigned platcov trial unblinded data available 800 patients provided 16 818 oropharyngeal viral quantitative pcr qpcr measurements 504 63 female 783 98 patients received least one vaccine dose 703 88 fully vaccinated sarscov2 viral clearance biphasic biexponential first phase accelerated effective interventions effective interventions studied maximum discriminative power maximum expected z score obtained evaluating serial data first 5 days enrolment 2year period studied median viral clearance halflives estimated 7 days shortened 166 h iqr 153 182 september 2021 92 h 80 106 october 2023 patients receiving antiviral drugs equivalent relative reduction 44 95 credible interval cri 19 64 parallel reduction viral clearance halflives time observed patients receiving antiviral drugs example 158 patients assigned ritonavirboosted nirmatrelvir 3380 qpcr measurements median viral clearance halflife reduced 64 h iqr 57 73 june 2022 48 h 42 55 october 2023 relative reduction 26 95 cri 4 42 sarscov2 viral clearance kinetics symptomatic vaccinated individuals accelerated substantially 2 years pandemic necessitating change new sarscov2 antivirals compared ie shortening period pharmacodynamic assessment writing october 2023 antiviral efficacy covid19 efficiently assessed vivo using serial qpcrs duplicate oropharyngeal swab eluates taken daily 5 days drug administration wellcome trust