Antivirals

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Antivirals

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This page undergoes regular review and was last comprehensively reviewed on November 1, 2022. Some sections may reflect more recent updates.

Overview

Antivirals are a class of drug that inhibit viral replication and are commonly used against influenza. According to NIH, antivirals’ role in COVID-19 treatment is to “inhibit viral entry via the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2); viral membrane fusion and endocytosis; or the activity of the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) and the RNA-dependent RNA polymerase. Because viral replication may be particularly active early in the course of COVID-19, antiviral therapy may have the greatest impact before the illness progresses to the hyperinflammatory state that can characterize the later stages of disease, including critical illness.”

Remdesivir (administered intravenously) was the first antiviral to be FDA-approved for the treatment of COVID-19 in October 2020. In December 2021, FDA granted the first emergency use authorization for an oral antiviral protease inhibitor for COVID-19, ritonavir-boosted nirmatrelvir (brand name Paxlovid), which was followed closely by EUA approval for molnupiravir. Both have been studied in a variety of clinical trials.

The table below compares efficacy measures for antivirals among a variety of outpatient therapeutics for COVID-19.

Comparison of Antivirals for COVID-19: Prevention of Hospitalization or Death

 

NIRMATRELVIR/ RITONAVIR

MOLNUPIRAVIR

[REMDESIVIR] x 3 days (PINE-TREE Study)

Time from Symptom Onset (days)

5

5

7

~Cost for a course

$529

$700

$1872

Incidence (drug)

8/1039 (0.77%)

48/709 (6.77%)

 2/279 (0.7%)

 

Incidence (placebo)

66/1046 (6.3%)

 

68/699 (9.72%)

 

15/283 (5.3%)

 

Absolute RR (Risk difference)

5.5%

(p<0.0001)

 

2.95%

(-5.9 to -0.1)

 

4.6%

 

Relative RR (RRR)

88%

 

30.3%

 

87%

 

Hazard Ratio (95% CI)

0.12

 

0.69 (0.48-1.01)

 

0.13 (0.03-0.59)

P=0.008

 

Number Needed to Treat (NNT)

18

 

33.8

 

21.7

 


Molnupiravir

Molnupiravir (brand name Lagevrio) has been FDA-authorized for emergency use to treat mild-to-moderate COVID-19 since December 2021.

In ambulatory adult patients with mild-to-moderate COVID-19 at high risk for progression to severe disease who have no other treatment options, IDSA guidelines suggest molnupiravir be initiated within 5 days of symptom onset (conditional recommendation, low certainty of evidence). NIH guidelines also suggest molnupiravir only when other antiviral options cannot be used (class CIII recommendation).

For further information, refer to our standalone Molnupiravir page.

Nirmatrelvir/Ritonavir (Paxlovid)

Ritonavir-boosted nirmatrelvir (brand name Paxlovid) has been FDA-authorized for emergency use to treat mild-to-moderate COVID-19 since December 2021.

For ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, IDSA and NIH guidelines suggest ritonavir-boosted nirmatrelvir treatment initiation within five days of symptom onset.

For further information, refer to our standalone Ritonavir-Boosted Nirmatrelvir (Paxlovid) page.

Remdesivir

Remdesivir (brand name Veklury) has been FDA-approved for the treatment of COVID-19 in hospitalized adults and children 12 years and older since
October 2020 and FDA-authorized for emergency use in certain outpatient and pediatric populations since January 2022. 

In inpatients on supplemental oxygen but not on mechanical ventilation or ECMO, IDSA guidelines suggests treatment with five days of remdesivir rather than 10 days of remdesivir (conditional recommendation, low certainty of evidence). In inpatients with COVID-19 admitted to the hospital without the need for supplemental oxygen and oxygen saturation >94% on room air, the IDSA panel suggests against the routine use of remdesivir (conditional recommendation, very low certainty of evidence).

Among ambulatory patients with mild-to-moderate COVID-19 at high risk for progression to severe disease, IDSA guidelines suggest remdesivir for 3 days, initiated within 7 days of symptom onset, rather than no remdesivir (conditional recommendation, low certainty of evidence).

For further information, refer to our standalone Remdesivir page.


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