Efficacy of Nirmatrelvir-Ritonavir versus Azvudine for COVID-19 Treatment in Tibet: A Retrospective Study
Xiang Zhao, Yuan Cheng, Meng Zhang, Bianba Qianda, Baima Zhouma, Bianba Yangzhen, Yao Zheng, Shuo Zhang, Huiying Zhao
Infection and Drug Resistance, doi:10.2147/idr.s423725
Background: Nirmatrelvir-ritonavir, also known as paxlovid, is a widely used antiviral drug against coronavirus disease 2019 (COVID-19). Azvudine, a drug previously used to treat human immunodeficiency virus-1, has also been used to treat COVID-19 in China. However, only a few clinical studies have evaluated the effects of azvudine. Additionally, studies comparing nirmatrelvirritonavir with azvudine have been limited in number. Methods: We carried out a retrospective case-control analysis at the Third People's Hospital of the Tibet Autonomous Region. Eighty-two eligible patients with COVID-19 who received azvudine treatment were included. A total of 145 control patients who received nirmatrelvir-ritonavir treatment were selected by propensity score matching for age, sex, the severity of disease, and initial cycle threshold values. A comparison of the nucleic acid test negative conversion time, the length of hospitalization, and mortality rate was conducted. Results: Overall, the mean nucleic acid test negative conversion time was comparable between the nirmatrelvir-ritonavir and azvudine groups (7.0 [11.0, 15.0] vs 9.0 [6.0, 12.0] days, P=0.064). However, for patients with mild COVID-19, the nucleic acid test negative conversion time was significantly shorter in the nirmatrelvir-ritonavir group than in the azvudine group (6.0 [5.0, 8.0] vs 8.0 [6.0, 11.0] days, P=0.029). The nirmatrelvir-ritonavir group and the azvudine group did not differ significantly in length of hospitalization (8.0 [5.5,10.5] vs 8.0 [5.0,10.0] days, P=0.378). Regarding the mortality rate, there were 4 (2.8%) deaths in the nirmatrelvir-ritonavir group and 3 (3.7%) in the azvudine group (P=0.706).
Conclusion: Azvudine is generally as effective as nirmatrelvir-ritonavir, but for patients with mild COVID-19, nirmatrelvir-ritonavir could suppress the virus more rapidly. For those who cannot be treated with nirmatrelvir-ritonavir, azvudine might be an effective therapy for COVID-19.
Patient Consent Statement The research on patients was approved by the Third People's Hospital of the Tibet Autonomous Region Clinical Research Ethics Committee, approval number ME-TBHP-23-03. All patients in the retrospective cohort study were anonymous, and the individual informed consent was not required. The Third People's Hospital of the Tibet Autonomous Region specifically waived the requirement for informed consent.
Author Contributions All authors made a significant contribution to the work reported, whether that was in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all the following areas; took part in drafting, revised or critically reviewed the article; approved final version of the manuscript; agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.
Disclosure The authors declare no conflicts of interest in this work.
References
Arias-Reyes, Carvajal-Rodriguez, Poma-Machicao, Decreased incidence, virus transmission capacity, and severity of COVID-19 at altitude on the American continent, PLoS One,
doi:10.1371/journal.pone.0237294Beasley, Price of COVID treatments from Pfizer, Merck, GSK align with patient benefits-report, Reuters Healthc Pharmaceuticals
Da Silva, Cabral, Souza, Serial viral load analysis by DDPCR to evaluate FNC efficacy and safety in the treatment of mild cases of COVID-19, Front Med,
doi:10.3389/fmed.2023.1143485Fernandes, Inchakalody, Merhi, Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis, therapeutics and vaccines, Ann Med,
doi:10.1080/07853890.2022.2031274Gao, Luo, Ren, Antiviral effect of azvudine and nirmatrelvir-ritonavir among hospitalized patients with COVID-19, J Infect,
doi:10.1016/j.jinf.2023.03.023Hammond, Leister-Tebbe, Gardner, Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2118542Liu, Wang, Zhou, Zhao, Zhang et al., Potential Role of ACE2 in Coronavirus Disease 2019 (COVID-19) Prevention and Management, J Transl Int Med,
doi:10.2478/jtim-2020-0003Marzolini, Kuritzkes, Marra, Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications, Clin Pharmacol Ther,
doi:10.1002/cpt.2646Najjar-Debbiny, Gronich, Weber, Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients, Clin Infect Dis,
doi:10.1093/cid/ciac443Ren, Luo, Yu, A Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study, Adv Sci,
doi:10.1002/advs.202001435Segovia-Juarez, Castagnetto, Gonzales, High altitude reduces infection rate of COVID-19 but not case-fatality rate, Respir Physiol Neurobiol,
doi:10.1016/j.resp.2020.103494Shang, Pan, Yang, Expert Consensus on the Diagnosis and Treatment of Critically Ill Patients with COVID-19 at High Altitudes in China, Chin J Crit Care Intensive Care Med
Steele, Couture, Reed, Estimated Number of COVID-19 Infections, Hospitalizations, and Deaths Prevented Among Vaccinated Persons in the US, December 2020 to September 2021, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2022.20385Stephens, Chernyavskiy, Bruns, Impact of altitude on COVID-19 infection and death in the United States: a modeling and observational study, PLoS One,
doi:10.1371/journal.pone.0245055Sun, Dian, epidemiology of antibiotic resistance and the mechanisms of resistance development and diffusion in both hospitals and the community,
doi:10.1016/j.eclinm.2023.101981Wang, Zhao, Chen, Liu, Feng, The effect of nirmatrelvir-ritonavir on viral clearance and length of hospital stay in patients infected with SARS-CoV-2 omicron variants, Influenza Other Respir Viruses,
doi:10.1111/irv.13095Zhang, Li, Wang, Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients, Signal Transduct Target Ther,
doi:10.1038/s41392-021-00835-6Zheng, Yu, Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study, BMJ,
doi:10.1136/bmj.m1443{ 'indexed': {'date-parts': [[2023, 9, 12]], 'date-time': '2023-09-12T22:42:03Z', 'timestamp': 1694558523324},
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'from: '
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'Accessed September 6, 2023.'},
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'DOI': '10.1093/cid/ciac443',
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'author': 'Najjar-Debbiny',
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'journal-title': 'Clin Infect Dis'},
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'DOI': '10.1056/NEJMoa2118542',
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'DOI': '10.1111/irv.13095',
'volume': '17',
'author': 'Wang',
'year': '2023',
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'first-page': '1191',
'DOI': '10.1002/cpt.2646',
'volume': '112',
'author': 'Marzolini',
'year': '2022',
'journal-title': 'Clin Pharmacol Ther'},
{ 'key': 'ref8',
'first-page': '56',
'author': 'Beasley',
'year': '2022',
'journal-title': 'Reuters Healthc Pharmaceuticals'},
{ 'key': 'ref9',
'doi-asserted-by': 'publisher',
'first-page': '2055',
'DOI': '10.3390/biomedicines11072055',
'volume': '11',
'author': 'Lee',
'year': '2023',
'journal-title': 'Biomedicines'},
{ 'key': 'ref10',
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'DOI': '10.1016/j.xinn.2022.100321',
'volume': '3',
'author': 'Yu',
'year': '2022',
'journal-title': 'Innovation'},
{ 'key': 'ref11',
'doi-asserted-by': 'publisher',
'first-page': '236',
'DOI': '10.1038/s41392-020-00351-z',
'volume': '5',
'author': 'Yu',
'year': '2020',
'journal-title': 'Signal Transduct Target Ther'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'first-page': '414',
'DOI': '10.1038/s41392-021-00835-6',
'volume': '6',
'author': 'Zhang',
'year': '2021',
'journal-title': 'Signal Transduct Target Ther'},
{ 'key': 'ref13',
'unstructured': 'National Health Commission of the People’s Republic of China. Diagnosis '
'and treatment plan for COVID-19 (trial version 9. Int J Epidemiol Infect '
'Dis. 2022;49:73–80.'},
{ 'key': 'ref14',
'first-page': '1',
'author': 'Shang',
'year': '2020',
'journal-title': 'Chin J Crit Care Intensive Care Med'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'first-page': '387',
'DOI': '10.1038/s41392-022-01249-8',
'volume': '7',
'author': 'Lei',
'year': '2022',
'journal-title': 'Signal Transduct Target Ther'},
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'doi-asserted-by': 'publisher',
'first-page': '115503',
'DOI': '10.1016/j.ejmech.2023.115503',
'volume': '257',
'author': 'Yang',
'year': '2023',
'journal-title': 'Eur J Med Chem'},
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'first-page': 'e2001435',
'DOI': '10.1002/advs.202001435',
'volume': '7',
'author': 'Ren',
'year': '2020',
'journal-title': 'Adv Sci'},
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'doi-asserted-by': 'publisher',
'first-page': '1143485',
'DOI': '10.3389/fmed.2023.1143485',
'volume': '10',
'author': 'da Silva',
'year': '2023',
'journal-title': 'Front Med'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'first-page': 'e158',
'DOI': '10.1016/j.jinf.2023.03.023',
'volume': '86',
'author': 'Gao',
'year': '2023',
'journal-title': 'J Infect'},
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'journal-title': 'Respir Physiol Neurobiol'},
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'volume': '8',
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'DOI': '10.1371/journal.pone.0245055',
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