Caution required on suggestions that antiretrovirals (ARVs) may be active against SARS-CoV-2: trial results to date are negative and maintaining supplies of ARVs for people living with HIV must be prioritized

New York City, March 25, 2020 – Treatment Action Group (TAG) is urging caution regarding the use of antiretroviral (ART) drugs as treatments for SARS-CoV-2/COVID-19. While there is clearly an acute need to carefully and quickly study interventions that may have activity against SARS-CoV-2, the virus which causes COVID-19 disease, it’s vitally important to be aware of the information that is currently available:

• Lopinavir/ritonavir (protease inhibitor, brand name KALETRA): Lopinavir has been reported to have activity against previously circulating coronaviruses SARS-CoV[1] and MERS-CoV.[2] A number of trials are evaluating lopinavir/ritonavir as a treatment for SARS-CoV-2 but the first published results indicate that it was not effective in hospitalized adults with severe COVID-19.[3] Negative results from a different trial involving people with mild/moderate COVID-19 have been published in preprint form.[4]
• Darunavir/cobicistat (protease inhibitor, brand name Prezcobix): As outlined in detail in a statement by the manufacturer Janssen,[5] an initial report of darunavir activity against SARS-CoV-2 in a laboratory dish involved a dose far higher than is achieved in the body. The company also reports that the drug does not bind well to SARS-CoV-2 protease, and—most importantly—that results from a randomized, controlled trial at the Shanghai Public Health Clinical Center (SPHCC) evaluating darunavir/cobicistat for the in treatment of COVID-19 showed that it was not effective.

TAG recommends the Interim Guidance for COVID-19 and Persons with HIV developed collectively by the HHS Antiretroviral and Opportunistic Infections Guidelines Panels and working groups of the Office of AIDS Research Advisory Council.[6] The guidance states:

“If protease inhibitors (PIs) are not already part of a person’s ARV [antiretroviral] regimen, their regimen should not be changed to include a PI to prevent or treat COVID-19, except in the context of a clinical trial and in consultation with an HIV specialist.”

Widespread off-label use of these antiretrovirals for COVID-19 is not supported by current data and could threaten to impede access for people living with HIV who need them as part of their treatment regimens.

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[1] Chu CM, Cheng VC, Hung IF, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252-256.

[2] de Wilde AH, Jochmans D, Posthuma CC, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 2014;58:4875-4884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136071/

[3] Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282. [Epub ahead of print] https://www.nejm.org/doi/full/10.1056/NEJMoa2001282

[4] Li Y, Xie Z, Lin W, et al. An exploratory randomized, controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI). medRxiv 2020.03.19.20038984; doi: https://doi.org/10.1101/2020.03.19.20038984

[5] Janssen Pharmaceutical Companies of Johnson & Johnson. Lack of evidence to support use of darunavir-based treatments for SARS-CoV-2. 2020 March 16. https://www.janssen.com/lack-evidence-support-use-darunavir-based-treatments-sars-cov-2

[6] U.S. Department of Health and Human Services Interim Guidance for COVID-19 and Persons with HIV. 2020 March 20. https://aidsinfo.nih.gov/guidelines/html/8/covid-19-and-persons-with-hiv–interim-guidance-/0

About TAG: Treatment Action Group (TAG) is an independent, activist and community-based research and policy think tank fighting for better treatment, prevention, a vaccine, and a cure for HIV, tuberculosis, and hepatitis C virus. TAG works to ensure that all people with HIV, TB, and HCV receive lifesaving treatment, care, and information. We are science-based treatment activists working to expand and accelerate vital research and effective community engagement with research and policy institutions.