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First-ever direct comparison between the two leading COVID antivirals molnupiravir and nirmatrelvir (Paxlovid®), published in The Lancet Infectious Diseases by NDM's Mahidol Oxford Tropical Medicine Research Unit (MORU) researchers reported that, while both drugs worked, nirmatrelvir (Paxlovid®) was more effective, clearing the virus from the throat more rapidly than molnupiravir.

This Lancet Infectious Diseases study, involved recruiting 209 patients in the Faculty of Tropical Medicine, Mahidol University, Thailand. The researchers from the Mahidol Oxford Tropical Medicine Research Unit (MORU) found that although the estimated mean rate of SARS-CoV-2 viral clearance with molnupiravir was 37% faster than no study drug, viral clearance was 84% faster with ritonavir-boosted nirmatrelvir.

Professor Sir Nick White, Professor of Tropical Medicine at the Mahidol Oxford Tropical Medicine Research Unit and co-principal investigator of the study, said: 'Nirmatrelvir (Paxlovid®) is clearly the most active antiviral drug tested to date in the PLATCOV platform trial, but it has some disadvantages: its companion ritonavir is associated with drug interactions and, like others, we documented rebounds of COVID after stopping the five-day course.'

Noting that there have been no direct comparisons before between these and other antiviral COVID medicines – despite the billions of dollars spent on them – the Mahidol-based University of Oxford affiliated researchers developed a simple method of quickly assessing the antiviral activity of COVID drugs in people with mild infections based on frequent measurements of the amount of virus at the back of the mouth.

In 2021, they started PLATCOV – a series of studies to compare all the antiviral drugs that were being used to treat COVID-19 infections.

Dr William Schilling, DPhil student at MORU in Bangkok and the first author, co-PI of the study, said: 'It is surprising that with so much attention and concern over COVID-19, and so much money spent, that direct head to head comparisons between medicines have not been conducted to inform public healthcare spending and guidelines.'

This testing method sets the stage for future rapid comparisons of antiviral drugs for COVID.

Dr Podjanee Jittamala, a Research Physician in MORU’s Clinical Therapeutic Unit, and joint first author of the study, said: 'The PLATCOV platform is a simple, well tolerated method of comparing antiviral drugs in patients with mild infections. It provides critical information on antiviral activity. COVID-19 is still common – and large clinical trials are expensive and take time. We cannot be sure that COVID will not become serious again, so we need methods of comparing medicines rapidly to inform treatment guidelines.'

Read the publication 'Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial' on The Lancet Infectious Diseases website.

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