Is acyclovir equivalent to Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment?

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Last updated: April 1, 2025View editorial policy

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From the Guidelines

No, acyclovir is not equivalent to Paxlovid for COVID-19 treatment. Acyclovir is an antiviral medication specifically designed to treat herpes virus infections such as herpes simplex, chickenpox, and shingles, and has no proven effectiveness against SARS-CoV-2, the virus that causes COVID-19. Paxlovid, which consists of nirmatrelvir and ritonavir, is specifically authorized for COVID-19 treatment and works by inhibiting a key enzyme (protease) that the coronavirus needs to replicate. According to the latest evidence from the American College of Physicians 1, Paxlovid is recommended for outpatient treatment of adults with confirmed COVID-19 at high risk for progressing to severe disease. The evidence supports the use of nirmatrelvir–ritonavir combination therapy, as it has been shown to reduce the risk of COVID-19 hospital admission and serious adverse events 1.

Key Differences Between Acyclovir and Paxlovid

  • Mechanism of action: Acyclovir interferes with DNA synthesis in herpes viruses, while Paxlovid inhibits a key enzyme (protease) that the coronavirus needs to replicate.
  • Indication: Acyclovir is used to treat herpes virus infections, while Paxlovid is specifically authorized for COVID-19 treatment.
  • Efficacy: Paxlovid has been shown to reduce the risk of COVID-19 hospital admission and serious adverse events, while acyclovir has no proven effectiveness against SARS-CoV-2.

Recommendations for COVID-19 Treatment

  • Paxlovid is the preferred treatment option for COVID-19, particularly for patients at high risk of progressing to severe disease.
  • Acyclovir should not be used as a substitute for Paxlovid in the treatment of COVID-19.
  • Patients with confirmed COVID-19 should be treated with evidence-based therapies, such as Paxlovid, under the guidance of a healthcare professional.

From the Research

Comparison of Acyclovir and Paxlovid for COVID-19 Treatment

  • There is no direct comparison between acyclovir and Paxlovid in the provided studies, as they focus on the efficacy and safety of Paxlovid (nirmatrelvir/ritonavir) for the treatment of COVID-19 2, 3, 4, 5, 6.
  • Acyclovir is an antiviral medication commonly used to treat herpes simplex virus infections, not COVID-19.
  • Paxlovid, on the other hand, is a specific treatment for COVID-19, authorized for use in patients with mild to moderate disease at high risk of progression to severe disease 2, 3, 4, 5, 6.
  • The studies demonstrate the efficacy of Paxlovid in reducing the risk of hospitalization and death in high-risk patients with COVID-19 3, 4, 5, 6.
  • There is no evidence to suggest that acyclovir is equivalent to Paxlovid for COVID-19 treatment, as they have different mechanisms of action and are used to treat different viral infections.

Efficacy of Paxlovid for COVID-19 Treatment

  • Paxlovid has been shown to reduce the risk of hospitalization and death in high-risk patients with COVID-19 by 89% compared to placebo 5.
  • A systematic review and meta-analysis found that Paxlovid significantly reduced the risk of hospitalization, all-cause mortality, and intensive care unit admission compared to control groups 3.
  • Real-world data from a population-based study in Israel found that Paxlovid was effective in reducing the risk of severe COVID-19 or mortality, particularly in older patients, immunosuppressed patients, and those with underlying neurological or cardiovascular disease 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Paxlovid for the treatment of COVID-19: a systematic review and meta-analysis.

Journal of infection in developing countries, 2024

Research

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.

The Cochrane database of systematic reviews, 2022

Research

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

The New England journal of medicine, 2022

Research

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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