Population-level Estimation #1: Safety of HIV/HepC protease inhibitors

Albert Prats University of Oxford SARS-CoronaVirus-2 A little piece of enveloped RNA!

Antiviral searches globally 120

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Antiviral drugs, non-specific

Activate cytoplasmic enzymes affecting viral messenger RNA translation Interferons and protein synthesis; evidence of minor efficacy in MERS-CoV in 4 combination with ribavirin

Antiviral drugs, antiretrovirals

ASC09 HIV protease inhibitor; to be used in combination with ritonavir 4

Azvudine Azidocytidine nucleoside analogue; HIV reverse transcriptase inhibitor 4 Hepatitis C virus NS3 protease inhibitor; to be used in combination with Danoprevir 1 ritonavir HIV protease inhibitor; used in combination with cobicistat, a CYP3A Darunavir 2 inhibitor Both HIV reverse transcriptase inhibitors; ritonavir is mainly used to Lopinavir + enhance the action of other drugs by inhibition of CYP3A4; in vitro and 2 ritonavir possible clinical efficacy in SARS-CoV

Nucleotide analogue; inhibitor of RNA-dependent RNA polymerase; used Remdesivir to treat Ebola and Marburg viruses; effective in vitro against SARS-CoV-1 2 and MERS and blocks infection with 2019-nCoV in vitro

Adapted from: https://www.cebm.net/covid-19/registered-trials-and-analysis/ at 29-March Antivirals Background

HIV antivirals Hepatitis C antivirals

in-vitro Effectiveness SARS Does it work? X SARS ? COVID ? COVID

Safety Gastrointestinal events Arrythmia Does it harm Liver Injury Liver Injury patients? Pancreatitis Hematologic etc … etc … Safety Does it harm HIV Antivirals Estimation patients?

Ritonavir/lopinavir SCCS All HIV protease inhibitors

VS

NNRTIs Cohort study of HIV treatment naïve patients Integrase inhibitors (PS stratification) Effectiveness Does it work? HIV Antivirals Estimation

Cohort study Ritonavir/lopinavir of SARS-CoV-2 Patients (PS stratification) All HIV protease inhibitors Hospital treated VS pneumonia Hydroxychloroquine Poor outcomes Safety Does it harm Hep C Antivirals Estimation patients?

Hepatitis C SCCS protease inhibitors

Peginterferon alfa-2b Cohort study Pairwise Comparisons Ribavirin (PS stratification) Effectiveness Does it work? Hep C Antivirals Estimation

Hepatitis C Cohort study pairwise protease inhibitors comparisons of SARS-CoV-2 Patients (PS stratification) Peginterferon alfa-2b Hospital treated pneumonia Ribavirin Poor pneumonia outcomes

Hydroxychloroquine Progress

Protocol Done!

SCCS Safety Analyses Cohorts

Effectiveness Analyses Cohorts

Background Paper writing and methods