While several antivirals have been considered among the candidate repurposed drugs against SARS-CoV-2 infection, limited evidence exists on Atazanavir/Ritonavir.
This trial was designed to assess the efficacy of Atazanavir/Ritonavir compared to Lopinavir/Ritonavir, another antiretroviral drug investigated in the previous studies.
This randomized, double-blind clinical trial was conducted on hospitalized patients with laboratory or confirmed SARS CoV-2 infection. Patients were randomly assigned (1:1) to receive either Lopinavir/Ritonavir (200mg Lopinavir+50mg Ritonavir, twice a day) or Atazanavir/Ritonavir (300mg Atazanavir+100 mg Ritonavir, once a day) for up to 14 days during their admission along with the standard care. The primary endpoint was total all-cause death in all patients during the hospitalization period. Secondary outcomes included length of hospitalization.
Out of 103 adults included in the analysis 54 and 49 were assigned to Atazanavir/Ritonavir and Lopinavir/Ritonavir groups, respectively. The occurrence of adverse effects, defined as symptoms attributed to the drugs which no longer appear upon the cessation of the drug, was higher for cardiac side effects in Atazanavir/Ritonavir group. No statistically significant difference was observed between the two groups in terms of the length of hospitalization. After adjustment for other covariates in the study, treatment with Atazanavir/ritonavir did not result in a significant reduction in mortality compared to treatment with Lopinavir/Ritonavir.
The efficacy of Atazanavir/Ritonavir in this preliminary study was not superior to Lopinavir/Ritonavir in reducing mortality and length of hospitalization in COVID-19 patients. However, the limited efficacy of both compounds does not support their use in primary care for COVID-19 patients.
- Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-99. doi: 10.1056/NEJMoa2001282.
- Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3. [PubMed: 32171076].
- Chu CM, Cheng VCC, Hung IFN, Wong MML, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59(3):252-6. doi: 10.1136/thorax.2003.012658. [PubMed: 14985565].
- Fintelman-Rodrigues N, Sacramento CQ, Ribeiro Lima C, Souza da Silva F, Ferreira AC, Mattos M, et al. Atazanavir, Alone or in Combination with Ritonavir, Inhibits SARS-CoV-2 Replication and Proinflammatory Cytokine Production. Antimicrob Agents Chemother. 2020;64(10):1-12. doi: 10.1128/AAC.00825-20. [PubMed: 32759267].
- Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, et al. Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial. Med. 2020;1(1):105-13. doi: 10.1016/j.medj.2020.04.001. [PubMed: 32838353].
- Consortium WST, Peto H, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Karim QA, et al. Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results. N Engl J Med. 2020;384(6):497-511. doi: 10.1056/NEJMoa2023184. [PubMed: 33264556].
- Mahanta S, Chowdhury P, Gogoi N, Goswami N, Borah D, Kumar R, et al. Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach. J Biomol Struct Dyn. 2021;39(10):3802-11. doi: 10.1080/07391102.2020.1768902. [PubMed: 32406317].
- Lv Z, Chu Y, Wang Y. HIV protease inhibitors: a review of molecular selectivity and toxicity. HIV AIDS. 2015;7:95-104. doi: 10.2147/HIV.S79956. [PubMed: 25897264].
- Stanley TL, Joy T, Hadigan CM, Liebau JG, Makimura H, Chen CY, et al. Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on muscle glucose uptake and visceral fat in HIV-infected patients. AIDS. 2009;23(11):1349-57. doi: 10.1097/QAD.0b013e32832ba904. [PubMed: 19474651]
- Shahab S, Sheikhi M, Alnajjar R, Saud SA, Khancheuski M, Strogova A. DFT investigation of atazanavir as potential inhibitor for 2019-nCoV coronavirus M protease. J Mol Struct. 2021;1228:129461. doi: 10.1016/j.molstruc.2020.129461. [PubMed: 33100379].
- Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2015;25(3):1057-73. doi: 10.1177/0962280215588241. [PubMed: 26092476].
- Beck BR, Shin B, Choi Y, Park S, Kang K. Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Comput Struct Biotechnol J. 2020;18:784-90. doi: 10.1016/j.csbj.2020.03.025. [PubMed: 32280433].
- Nekoukar Z, Ala S, Moradi S, Hill A, Davoudi Badabi AR, Alikhani A, et al. Comparison of the efficacy and safety of Atazanavir/Ritonavir plus Hydroxychloroquine with Lopinavir/Ritonavir plus Hydroxychloroquine in patients with moderate COVID-19, a randomized, double-blind clinical trial. Iran J Pharm Res. 2021;20(4):278-88. doi: 10.22037/ijpr.2021.115157.15243. [PubMed: 35194446].
- Kalantari S, Fard SR, Maleki D, Taher MT, Yassin Z, Alimohamadi Y, et al. Comparing the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients. J Med Virol. 2021;93(12):6557-65. doi: 10.1002/jmv.27195. [PubMed: 34255369].
- Thunström L, Newbold S, Finnoff D, Ashworth M, Shogren J. The Benefits and Costs of Using Social Distancing to Flatten the Curve for COVID-19. J Benefit-Cost Anal. 2020;11(2):179-95. doi:10.1017/bca.2020.12.
- Modelling WCCfID, Analysis MCfGID, Disease ALJIf, Analytics E, London IC. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand. WHO Geneva. 2020:1-20. doi: 10.25561/77482.
- Stübinger J, Schneider L. Epidemiology of coronavirus COVID-19: Forecasting the future incidence in different countries. Healthcare. 2020;8(2):1-15. doi: 10.3390/healthcare8020099. [PubMed: 32326512].
- Senanayake SL. Drug repurposing strategies for COVID-19. Drug Discov. 2020;2(2):1-3. doi: 10.4155/fdd-2020-0010.
- Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 — Final Report. N Engl J Med. 2020;383(19):1813-26. doi: 10.1056/NEJMoa2007764. [PubMed: 32445440].