• See Section 6.1 f or help t o identify patients at highest risk.
• Several therapeutic op tions are available: see decision support t ool that displays benefits and harms o f nirmatrelvir-ritonavir, molnupiravir and remdesivir.
• The GDG c oncluded that nirmatr elvir-ritonavir represents a superior choic e because it may hav e greater efficacy in preventing hospitalization than the alt ernatives; has f ewer concerns with respect t o harms than does molnupir avir; and is easier t o administer than intravenous remdesivir and the an tibodies.
• Clinicians should review all medic ations and no t consider nirmatrelvir-ritonavir in patients with possible dang erous drug interactions (note: man y drugs in teract with nirmatr elvir-ritonavir).
• Fully informed shared decision-making should det ermine whether nirmatr elvir-ritonavir should be used in pr egnant or breastfeeding w omen, given possible benefit and r esidual uncertainty regarding potential undesirable effects.
• Nirmatrelvir-ritonavir should be administ ered as soon as possible aft er onset o f symptoms, ideally within 5 day s.

Practical Info Route, dosage and duration: Additional considerations are available in three summaries of practical issues (nirmatrelvir-ritonavir for COVID-19, administration of nirmatrelvir-ritonavir for COVID-19, safety and monitoring f or patients receiving nirmatrelvirritonavir for COVID-19). Here follows a brief summary o f key points:

• The recommended dose f or nirmatrelvir-ritonavir is 300 mg (two 150 mg table ts) of nirmatrelvir and 100 mg o f ritonavir every 12 hours daily for 5 days, as per the r egimen evaluated in large trials informing the recommendation.
• In renal insufficiency (GFR 30–59 m L/min) the dose r eduction is 150 mg o f nirmatrelvir and 100 mg o f ritonavir every 12 hours daily for 5 days.
• Administration should be as early as possible in the time c ourse of the disease. I n the included studies, nirma trelvir-ritonavir was administered within 5 da ys of disease onse t. In any patient being c onsidered for nirmatrelvir-ritonavir use, clinicians need to giv e serious consideration to drug in teractions. The Liverpool COVID-19 drug interaction checker may be use ful in this regard (19).

Resources and other considerations Acceptability and feasibility Nirmatrelvir-ritonavir is unlikely to be a vailable for all individuals who, giv en the op tion, would choose to r eceive the treatment. This reinforces that nirmatrelvir-ritonavir should be reserved for those at higher risk. Obstacles to access in lo w- and middle-inc ome countries (LMICs) may prove formidable due to c ost and availability. Those with socioeconomic disadvantages tend to ha ve less ac cess to services, including diagnostic testing and tr eatments, in the first 5 days of symptoms, and thus less ac cess to the in terventions. Therefore, if pa tients at higher risk receive the intervention, this may exacerbate health inequity. It is important that countries integrate the COVID-19 clinical care pathway in the parts o f the health s ystem that may provide care for patients with non-se vere COVID-19 (i.e. primary care, community care settings). The recommendations should provide a stimulus to engag e all possible mechanisms to impr ove global access to the intervention. In promoting access, WHO has pr equalified generic versions of molnupiravir and one g eneric version of nirmatrelvir-ritonavir. In addition, there are additional applications under review for both products. United Nations (UN) partners procure these products and are making them a vailable to LMICs. WHO and UN partners support alloca tion and procurement mechanisms f or countries to ensure that these medicines are available and integrated into national supply chains. Individual countries may formulate their guidelines considering available resources and prioritize treatment options accordingly. Access to SARS-CoV-2 diagnostics: Since this recommendation involves ideally administering treatment with nirmatrelvirritonavir within 5 days of symptom onset, increasing access and ensuring appropriate use o f diagnostic tests is essen tial for implementation. Thus, availability and use of appropriate SARS-CoV-2 diagnostic tests is needed to impr ove access to drugs, especially those targeting the early phase o f disease. T he appropriate use o f rapid diagnostic tests such as antigen-detection assays can improve early diagnosis in the c ommunity and in primary health car e settings. Health care systems must, however, gain e xpertise in choosing and implemen ting rapid tests, choosing those most applicable to their settings.